Database of Pathogenic Variants

Variant Detail

Variant Information

ID: DPV: 395
Chromosome: 1
Gene
HGVS (GRCh37/hg19): NC_000001.10:g.41285137G>C
HGVS (GRCh38/hg38): NC_000001.11:g.40819465G>C
HGVS (RNA): NM_004700:c.827G>C
HGVS (Protein): NP_004691:p.W276S
dbSNP: -
ClinGen Allele Registry: CA340533
Allele Frequency

Individual Information

ID

DPVS:31.1

Clinical Significance

Pathogenic

Date Last Evaluated

2017-03-30

Clinical Significance Citation

Moteki, H. Comprehensive genetic testing with ethnic-specific filtering by allele frequency in a Japanese hearing-loss population. 2016 Clin Genet. 2016 Apr;89(4):466-472. doi: 10.1111/cge.12677. Epub 2015 Oct 6. PMID:26346818

Transcript

Disease

Partial deafness
MedGen:C0018772

Phenotype

Zygosity

single heterozygote

Allele Origin

inherited

Affected Status

yes

Sample Type

Analysis Type

Next-Generation Sequencing - Illumina/Solexa

Collection Method

research

Compound heterozygous variant(s)

Data Submitter

Comment

ID

DPVS:254.1

Clinical Significance

Pathogenic

Date Last Evaluated

2015-07-06

Clinical Significance Citation

Gao, Y. Impaired surface expression and conductance of the KCNQ4 channel lead to sensorineural hearing loss. 2013 J Cell Mol Med. 2013 Jul;17(7):889-900. doi: 10.1111/jcmm.12080. Epub 2013 Jun 11. PMID:23750663

Kim, H. J. Cellular and molecular mechanisms of autosomal dominant form of progressive hearing loss, DFNA2. 2011 J Biol Chem. 2011 Jan 14;286(2):1517-27. doi: 10.1074/jbc.M110.179010. Epub 2010 Oct 21. PMID:20966080

Usami, S. Simultaneous screening of multiple mutations by invader assay improves molecular diagnosis of hereditary hearing loss: a multicenter study. 2012 PLoS One. 2012;7(2):e31276. doi: 10.1371/journal.pone.0031276. Epub 2012 Feb 24. PMID:22384008

Mori, K. Social Health Insurance-Based Simultaneous Screening for 154 Mutations in 19 Deafness Genes Efficiently Identified Causative Mutations in Japanese Hearing Loss Patients. 2016 PLoS One. 2016 Sep 14;11(9):e0162230. doi: 10.1371/journal.pone.0162230. eCollection 2016. PMID:27627659

Akita, J. Clinical and genetic features of nonsyndromic autosomal dominant sensorineural hearing loss: KCNQ4 is a gene responsible in Japanese. 2001 J Hum Genet. 2001;46(7):355-61. doi: 10.1007/s100380170053. PMID:11450843

Transcript

Disease

Partial deafness
MedGen:C0018772

Phenotype

Zygosity

single heterozygote

Allele Origin

germline

Affected Status

yes

Sample Type

Analysis Type

SEQuencing

Collection Method

clinical testing

Compound heterozygous variant(s)

Data Submitter

Comment

ID

DPVS:1574.1

Clinical Significance

Pathogenic

Date Last Evaluated

2018-01-30

Clinical Significance Citation

Sakuma, N. An effective screening strategy for deafness in combination with a next-generation sequencing platform: a consecutive analysis. 2016 J Hum Genet. 2016 Mar;61(3):253-61. doi: 10.1038/jhg.2015.143. Epub 2016 Jan 14. PMID:26763877

Van Camp, G. A mutational hot spot in the KCNQ4 gene responsible for autosomal dominant hearing impairment. 2002 Hum Mutat. 2002 Jul;20(1):15-9. doi: 10.1002/humu.10096. PMID:12112653

Topsakal, V. Phenotype determination guides swift genotyping of a DFNA2/KCNQ4 family with a hot spot mutation (W276S). 2005 Otol Neurotol. 2005 Jan;26(1):52-8. PMID:15699719

Transcript

Disease

Deafness, autosomal dominant, 2A
OMIM:600101
MedGen:C2677637

Phenotype

Zygosity

single heterozygote

Allele Origin

germline

Affected Status

yes

Sample Type

Analysis Type

Next-Generation 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
1	41285137	NC_000001.10:g.41285137G>C	G	C	.	.	CLNALLELEID=21281;CLNDN=Autosomal_dominant_nonsyndromic_deafness_2A|Rare_genetic_deafness;CLNDISDB=MONDO:MONDO:0010817,MedGen:C2677637,OMIM:600101|MedGen:CN826980,Orphanet:ORPHA96210;CLNSIG=Pathogenic;CLNHGVS=NC_000001.10:g.41285137G>C;GENEINFO=6298:9132;DPVID=395;DPVSIG=Pathogenic;DPVDSDBID=MedGen:C0018772|OMIM:600101;DPVDBN=Partial_deafness|Deafness\x2c_autosomal_dominant\x2c_2A;DPVHGVS=NC_000001.10:g.41285137G>C	.

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-7oxpzun6>
##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
1	40819465	NC_000001.10:g.41285137G>C	G	C	.	.	dbSNP_RSID=rs80358277;CLNALLELEID=21281;CLNDN=Autosomal_dominant_nonsyndromic_deafness_2A|Rare_genetic_deafness;CLNDISDB=MONDO:MONDO:0010817,MedGen:C2677637,OMIM:600101|MedGen:CN826980,Orphanet:ORPHA96210;CLNSIG=Pathogenic;CLNHGVS=NC_000001.11:g.40819465G>C;GENEINFO=6298:9132;DPVID=395;DPVSIG=Pathogenic;DPVDSDBID=MedGen:C0018772|OMIM:600101;DPVDBN=Partial_deafness|Deafness\x2c_autosomal_dominant\x2c_2A;DPVHGVS=NC_000001.11:g.40819465G>C	.