Submissions for variant NM_032119.4(ADGRV1):c.7867G>A (p.Glu2623Lys)

gnomAD frequency: 0.00019  dbSNP: rs146526977

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000150763	SCV000198240	uncertain significance	not specified	2013-11-09	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The Glu2623Lys vari ant has not been previously reported in individuals with hearing loss, but has b een identified in 0.05% (2/4078) of African American chromosomes by the NHLBI Ex ome Sequencing Project and in 1% (2/192) of Luhya (Kenya) chromosomes by the 100 0 Genomes Project (http://evs.gs.washington.edu/EVS/; dbSNP rs146526977). Howeve r, these frequencies are not high enough to rule out a pathogenic role. Computat ional analyses (biochemical amino acid properties, conservation, AlignGVGD, Poly Phen2, and SIFT) do not provide strong support for or against an impact to the p rotein. In summary, the clinical significance of this variant cannot be determin ed with certainty; however based upon its frequency in the Luhya population, we would lean towards a more likely benign role.
Illumina Laboratory Services, Illumina	RCV001157104	SCV001318650	uncertain significance	Usher syndrome type 2C	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.
Invitae	RCV001312581	SCV001503040	likely benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001312581	SCV002056061	uncertain significance	not provided	2022-01-10	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002514899	SCV003759382	uncertain significance	Inborn genetic diseases	2022-02-09	criteria provided, single submitter	clinical testing	The c.7867G>A (p.E2623K) alteration is located in exon 33 (coding exon 33) of the ADGRV1 gene. This alteration results from a G to A substitution at nucleotide position 7867, causing the glutamic acid (E) at amino acid position 2623 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001312581	SCV001951656	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001312581	SCV001969799	uncertain significance	not provided		no assertion criteria provided	clinical testing