Submissions for variant NM_032119.4(ADGRV1):c.6317C>T (p.Ala2106Val) (rs186999408)

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine	RCV000039607	SCV000063296	benign	not specified	2012-04-30	criteria provided, single submitter	clinical testing	Ala2106Val in Exon 29 of GPR98: This variant is not expected to have clinical si gnificance because it has been identified in 0.7% (22/3118) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS).
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	RCV000039607	SCV000228732	benign	not specified	2014-06-06	criteria provided, single submitter	clinical testing
GeneDx	RCV000039607	SCV000321753	uncertain significance	not specified	2016-07-20	criteria provided, single submitter	clinical testing	The A2106V variant in the ADGRV1 gene has been reported previously in one individual with Usher syndrome; however, no information was provided about the presence or absence of any co-occurring variants in ADGRV1 or other Usher-related genes (Le Quesne et al., 2012). While not present in the homozygous state, the NHLBI ESP Exome Sequencing Project reports A2106V was observed in 27/3810 (0.71%) alleles from individuals of African American background, indicating it may be a rare variant in this population. The A2106V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret A2106V as a variant of uncertain significance.
Invitae	RCV000903694	SCV001048174	likely benign	not provided	2019-12-31	criteria provided, single submitter	clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000903694	SCV001154439	uncertain significance	not provided	2016-06-01	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV001155314	SCV001316736	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.