Submissions for variant NM_015404.4(WHRN):c.191C>A (p.Ala64Asp)

gnomAD frequency: 0.00053  dbSNP: rs146655362

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038882	SCV000062560	likely benign	not specified	2012-12-28	criteria provided, single submitter	clinical testing	Ala64Asp in exon 1 of DFNB31: This variant is not expected to have clinical sign ificance because it has been identified in 0.2% (15/8598) of European American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS/; dbSNP rs146655362).
Eurofins Ntd Llc (ga)	RCV000723700	SCV000113670	uncertain significance	not provided	2013-08-16	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000291435	SCV000476806	uncertain significance	Usher syndrome type 2D	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000346369	SCV000476807	uncertain significance	Autosomal recessive nonsyndromic hearing loss 31	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000723700	SCV001208506	uncertain significance	not provided	2024-01-29	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 64 of the WHRN protein (p.Ala64Asp). This variant is present in population databases (rs146655362, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with WHRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 45664). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen	RCV000723700	SCV004160627	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	WHRN: BS1:Supporting
Division of Human Genetics, Children's Hospital of Philadelphia	RCV000477861	SCV000536781	uncertain significance	Autosomal recessive nonsyndromic hearing loss 31; Usher syndrome type 2D	2015-10-13	no assertion criteria provided	research