Variant Detail

Variant Information
ID
DPV: 1137
Chromosome
19
Gene
HGVS (GRCh37/hg19)
NC_000019.9:g.18273784G>A
HGVS (GRCh38/hg38)
NC_000019.10:g.18162974G>A
HGVS (RNA)
NM_005027.3:c.1117G>A
HGVS (Protein)
NP_005018:p.G373R
dbSNP
-
ClinGen Allele Registry
CA130573
Allele Frequency
Individual Information

ID
DPVS:889.1
Clinical Significance
Pathogenic
Date Last Evaluated
2017-03-30
Clinical Significance Citation
Negishi, Y. A combination of genetic and biochemical analyses for the diagnosis of PI3K-AKT-mTOR pathway-associated megalencephaly. 2017 BMC Med Genet. 2017 Jan 13;18(1):4. doi: 10.1186/s12881-016-0363-6. PMID:28086757

Negishi Y. et al. BMC Med. Genet. in press (2017).

Transcript
-
Disease

megalencephaly

Phenotype
-
Zygosity
single heterozygote
Allele Origin
germline
Affected Status
yes
Sample Type
  • DNA
Analysis Type
  • Denaturing High-Performance Liquid Chromatography
Collection Method
literature only
Compound heterozygous variant(s)
Data Submitter
Comment
Targeted resequencing (15 mTOR pathway genes)

ID
DPVS:890.1
Clinical Significance
Pathogenic
Date Last Evaluated
2017-03-30
Clinical Significance Citation
Negishi, Y. A combination of genetic and biochemical analyses for the diagnosis of PI3K-AKT-mTOR pathway-associated megalencephaly. 2017 BMC Med Genet. 2017 Jan 13;18(1):4. doi: 10.1186/s12881-016-0363-6. PMID:28086757

Negishi Y. et al. BMC Med. Genet. in press (2017).

Transcript
-
Disease

megalencephaly

Phenotype
-
Zygosity
single heterozygote
Allele Origin
germline
Affected Status
yes
Sample Type
  • DNA
Analysis Type
  • Denaturing High-Performance Liquid Chromatography
Collection Method
literature only
Compound heterozygous variant(s)
Data Submitter
Comment
Targeted resequencing (15 mTOR pathway genes)

ID
DPVS:5948.1
Clinical Significance
Pathogenic
Date Last Evaluated
2018-12-04
Clinical Significance Citation
Negishi, Y. A combination of genetic and biochemical analyses for the diagnosis of PI3K-AKT-mTOR pathway-associated megalencephaly. 2017 BMC Med Genet. 2017 Jan 13;18(1):4. doi: 10.1186/s12881-016-0363-6. PMID:28086757

Negishi et al. BMC Med Genet 18:4, 2017

Transcript
-
Disease

Megalencephaly

Phenotype
-
Zygosity
single heterozygote
Allele Origin
de novo
Affected Status
yes
Sample Type
  • DNA
Analysis Type
  • SEQuencing
Collection Method
literature only
Compound heterozygous variant(s)
Data Submitter
Comment
-

ID
DPVS:6609.1
Clinical Significance
Pathogenic
Date Last Evaluated
2019-03-22
Clinical Significance Citation
Mirzaa, G. M. Characterisation of mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria: a next-generation sequencing study. 2015 Lancet Neurol. 2015 Dec;14(12):1182-95. doi: 10.1016/S1474-4422(15)00278-1. Epub 2015 Oct 29. PMID:26520804

Transcript
-
Disease

Phenotype
-
Zygosity
single heterozygote
Allele Origin
de novo
Affected Status
yes
Sample Type
  • DNA
Analysis Type
  • SEQuencing
Collection Method
literature only
Compound heterozygous variant(s)
Data Submitter
Comment
-

ID
DPVS:6610.1
Clinical Significance
Pathogenic
Date Last Evaluated
2019-03-22
Clinical Significance Citation
Mirzaa, G. M. Characterisation of mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria: a next-generation sequencing study. 2015 Lancet Neurol. 2015 Dec;14(12):1182-95. doi: 10.1016/S1474-4422(15)00278-1. Epub 2015 Oct 29. PMID:26520804

Transcript
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Disease

Phenotype
-
Zygosity
single heterozygote
Allele Origin
maternal
Affected Status
yes
Sample Type
  • DNA
Analysis Type
  • SEQuencing
Collection Method
literature only
Compound heterozygous variant(s)
Data Submitter
Comment
-

ID
DPVS:6611.1
Clinical Significance
Pathogenic
Date Last Evaluated
2019-03-22
Clinical Significance Citation
Mirzaa, G. M. Characterisation of mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria: a next-generation sequencing study. 2015 Lancet Neurol. 2015 Dec;14(12):1182-95. doi: 10.1016/S1474-4422(15)00278-1. Epub 2015 Oct 29. PMID:26520804

Transcript
-
Disease

Phenotype
-
Zygosity
single heterozygote
Allele Origin
inherited
Affected Status
yes
Sample Type
  • DNA
Analysis Type
  • SEQuencing
Collection Method
literature only
Compound heterozygous variant(s)
Data Submitter
Comment
-

ID
DPVS:6612.1
Clinical Significance
Pathogenic
Date Last Evaluated
2019-03-22
Clinical Significance Citation
Mirzaa, G. M. Characterisation of mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria: a next-generation sequencing study. 2015 Lancet Neurol. 2015 Dec;14(12):1182-95. doi: 10.1016/S1474-4422(15)00278-1. Epub 2015 Oct 29. PMID:26520804

Transcript
-
Disease

Phenotype
-
Zygosity
single heterozygote
Allele Origin
germline
Affected Status
yes
Sample Type
  • DNA
Analysis Type
  • SEQuencing
Collection Method
literature only
Compound heterozygous variant(s)
Data Submitter
Comment
-

ClinVar
Model Animals
VCF
VCF (GRCh37/hg19) 
											##fileformat=VCFv4.0
##reference=GRCh37
##INFO=<ID=CLNALLELEID,Number=1,Type=Integer,Description="the ClinVar Allele ID">
##INFO=<ID=CLNDISDB,Number=.,Type=String,Description="Tag-value pairs of disease database name and identifier, e.g. OMIM:NNNNNN (from ClinVar)">
##INFO=<ID=CLNDN,Number=.,Type=String,Description="ClinVar's preferred disease name for the concept specified by disease identifiers in CLNDISDB (from ClinVar)">
##INFO=<ID=CLNHGVS,Number=.,Type=String,Description="Top-level (primary assembly, alt, or patch) HGVS expression.(from ClinVar)">
##INFO=<ID=CLNSIG,Number=.,Type=String,Description="Clinical significance for this single variant (from ClinVar)">
##INFO=<ID=EXAC_AC,Number=A,Type=Integer,Description="Allele count in genotypes, for each ALT allele, in the same order as listed (from ExAC r1)">
##INFO=<ID=EXAC_AF,Number=A,Type=Float,Description="Allele Frequency, for each ALT allele, in the same order as listed (from ExAC r1)">
##INFO=<ID=EXAC_AN,Number=1,Type=Integer,Description="Total number of alleles in called genotypes (from ExAC r1)">
##INFO=<ID=EXAC_FILTER,Number=1,Type=String,Description="calculated by self of overlapping values in field FILTER (from ExAC r1)">
##INFO=<ID=GNOMAD_AC,Number=A,Type=Integer,Description="Allele count in genotypes, for each ALT allele, in the same order as listed (from gnomAD v2.1.1 )">
##INFO=<ID=GNOMAD_AF,Number=A,Type=Float,Description="Allele Frequency, for each ALT allele, in the same order as listed (from gnomAD v2.1.1 )">
##INFO=<ID=GNOMAD_AN,Number=1,Type=Integer,Description="Total number of alleles in called genotypes (from gnomAD v2.1.1 )">
##INFO=<ID=HGVD_AAF,Number=A,Type=Float,Description="Alternative Allele Frequency(s) NA/(NR+NAtotal) (from HGVD/DBexome20170802)">
##INFO=<ID=HGVD_AC,Number=A,Type=Integer,Description="number(s) of alternative allele(s) (from HGVD/DBexome20170802)">
##INFO=<ID=HGVD_NR,Number=1,Type=Integer,Description="number of reference allele (from HGVD/DBexome20170802)">
##INFO=<ID=TOMMO_4_7K_AC,Number=A,Type=Integer,Description="Allele count in genotypes (from ToMMo 4.7KJPN (20190826))">
##INFO=<ID=TOMMO_4_7K_AF,Number=A,Type=Float,Description="Allele frequency, for each ALT allele, in the same order as listed  (from ToMMo 4.7KJPN (20190826))">
##INFO=<ID=TOMMO_4_7K_AN,Number=1,Type=Integer,Description="Total number of alleles in called genotypes (from ToMMo 4.7KJPN (20190826))">
##INFO=<ID=dbSNP_RSID,Number=1,Type=String,Description="dbSNP ID (from dbSNP b151 )">
##INFO=<ID=GENEINFO,Number=1,Type=String,Description="Pairs each of gene symbol:gene id. The gene symbol and id are delimited by a colon (:)">
##INFO=<ID=DPVID,Number=.,Type=String,Description="DPV Variant ID">
##INFO=<ID=DPVSIG,Number=.,Type=String,Description="Variant Clinical Significance">
##INFO=<ID=DPVDSDBID,Number=.,Type=String,Description="Variant disease database ID">
##INFO=<ID=DPVDBN,Number=.,Type=String,Description="Variant disease name">
##INFO=<ID=DPVHGVS,Number=.,Type=String,Description="Variant in HGVS.">
#CHROM	POS	ID	REF	ALT	QUAL	FILTER	INFO
19	18273784	NC_000019.9:g.18273784G>A	G	A	.	.	CLNALLELEID=48407;CLNDN=Megalencephaly-capillary_malformation-polymicrogyria_syndrome|Megalencephaly-polymicrogyria-polydactyly-hydrocephalus_syndrome_1|Inborn_genetic_diseases|not_provided;CLNDISDB=MONDO:MONDO:0011240,MedGen:C1865285,OMIM:602501,Orphanet:ORPHA60040|MONDO:MONDO:0011313,MedGen:C4012727,OMIM:603387|MeSH:D030342,MedGen:C0950123|MedGen:CN517202;CLNSIG=Pathogenic/Likely_pathogenic;CLNHGVS=NC_000019.9:g.18273784G>A;dbSNP_RSID=rs940576598;GENEINFO=8980:5296;DPVID=1137;DPVSIG=Pathogenic;DPVDSDBID=OMIM:602501|OMIM:603387;DPVDBN=Megalencephaly-capillary_malformation-polymicrogyria_syndrome|Megalencephaly-polymicrogyria-polydactyly-hydrocephalus_syndrome_1;DPVHGVS=NC_000019.9:g.18273784G>A	.
VCF (GRCh38/hg38) 
											##fileformat=VCFv4.0
##reference=GRCh38
##INFO=<ID=CLNALLELEID,Number=1,Type=Integer,Description="the ClinVar Allele ID">
##INFO=<ID=CLNDISDB,Number=.,Type=String,Description="Tag-value pairs of disease database name and identifier, e.g. OMIM:NNNNNN (from ClinVar)">
##INFO=<ID=CLNDN,Number=.,Type=String,Description="ClinVar's preferred disease name for the concept specified by disease identifiers in CLNDISDB (from ClinVar)">
##INFO=<ID=CLNHGVS,Number=.,Type=String,Description="Top-level (primary assembly, alt, or patch) HGVS expression.(from ClinVar)">
##INFO=<ID=CLNSIG,Number=.,Type=String,Description="Clinical significance for this single variant (from ClinVar)">
##INFO=<ID=GNOMAD_AC,Number=A,Type=Integer,Description="Allele count in genotypes, for each ALT allele, in the same order as listed (from gnomAD v2.1.1 )">
##INFO=<ID=GNOMAD_AF,Number=A,Type=Float,Description="Allele Frequency, for each ALT allele, in the same order as listed (from gnomAD v2.1.1 )">
##INFO=<ID=GNOMAD_AN,Number=1,Type=Integer,Description="Total number of alleles in called genotypes (from gnomAD v2.1.1 )">
##INFO=<ID=dbSNP_RSID,Number=1,Type=String,Description="dbSNP ID (from dbSNP b151 )">
##originalFile=</tmp/crossmap-input-gangpb5y>
##targetRefGenome=</usr/lib64/python2.7/site-packages/transvar/transvar.download/hg38.fa>
##INFO=<ID=GENEINFO,Number=1,Type=String,Description="Pairs each of gene symbol:gene id. The gene symbol and id are delimited by a colon (:)">
##INFO=<ID=DPVID,Number=.,Type=String,Description="DPV Variant ID">
##INFO=<ID=DPVSIG,Number=.,Type=String,Description="Variant Clinical Significance">
##INFO=<ID=DPVDSDBID,Number=.,Type=String,Description="Variant disease database ID">
##INFO=<ID=DPVDBN,Number=.,Type=String,Description="Variant disease name">
##INFO=<ID=DPVHGVS,Number=.,Type=String,Description="Variant in HGVS.">
#CHROM	POS	ID	REF	ALT	QUAL	FILTER	INFO
19	18162974	NC_000019.9:g.18273784G>A	G	A	.	.	dbSNP_RSID=rs587776934;CLNALLELEID=48407;CLNDN=Megalencephaly-capillary_malformation-polymicrogyria_syndrome|Megalencephaly-polymicrogyria-polydactyly-hydrocephalus_syndrome_1|Inborn_genetic_diseases|not_provided;CLNDISDB=MONDO:MONDO:0011240,MedGen:C1865285,OMIM:602501,Orphanet:ORPHA60040|MONDO:MONDO:0011313,MedGen:C4012727,OMIM:603387|MeSH:D030342,MedGen:C0950123|MedGen:CN517202;CLNSIG=Pathogenic/Likely_pathogenic;CLNHGVS=NC_000019.10:g.18162974G>A;GENEINFO=8980:5296;DPVID=1137;DPVSIG=Pathogenic;DPVDSDBID=OMIM:602501|OMIM:603387;DPVDBN=Megalencephaly-capillary_malformation-polymicrogyria_syndrome|Megalencephaly-polymicrogyria-polydactyly-hydrocephalus_syndrome_1;DPVHGVS=NC_000019.10:g.18162974G>A	.