Submissions for variant NM_015404.4(WHRN):c.2384G>A (p.Arg795Gln)

gnomAD frequency: 0.00010  dbSNP: rs143763650

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000825268	SCV000966560	likely benign	not specified	2018-09-13	criteria provided, single submitter	clinical testing	The p.Arg795Gln variant in WHRN is classified as likely benign due to a lack of conservation across species. At least 6 mammalian species have a Glutamine (Gln) at this position. In addition, computational prediction tools predict that this variant does not impact the protein. The variant has also been identified in 0. 2% (73/30782) of South Asian chromosomes, including two homozygotes, by gnomAD ( http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BP4_Strong, BS1_Su pporting.
Illumina Laboratory Services, Illumina	RCV001169713	SCV001332477	uncertain significance	Usher syndrome type 2D	2018-01-13	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	RCV001169714	SCV001332478	uncertain significance	Autosomal recessive nonsyndromic hearing loss 31	2018-01-13	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	RCV001510640	SCV001717734	benign	not provided	2025-01-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001510640	SCV001795594	likely benign	not provided	2020-07-27	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001510640	SCV001927375	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001510640	SCV001975435	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003975338	SCV004788108	likely benign	WHRN-related disorder	2022-10-05	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).