Submissions for variant NM_032119.4(ADGRV1):c.6443C>T (p.Ala2148Val)

gnomAD frequency: 0.00022  dbSNP: rs375921325

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039609	SCV000063298	likely benign	not specified	2013-02-19	criteria provided, single submitter	clinical testing	Ala2148Val in exon 29 of GPR98: This variant is not expected to have clinical si gnificance because it is has been identified in 3/3124 (0.09%) African American chromosomes from a broad population by the NHLBI Exome sequencing project (http: //evs.gs.washington.edu/EVS/) and due to a lack of conservation across species, including mammals. Of note, possum has a valine (Val) at this position despite h igh nearby amino acid conservation. In addition, this variant has now been ident ified in our laboratory in two individuals, neither of whom had a second GPR98 v ariant.
Eurofins Ntd Llc (ga)	RCV000724387	SCV000228734	uncertain significance	not provided	2015-01-16	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000724387	SCV001537753	benign	not provided	2024-12-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000724387	SCV002498919	uncertain significance	not provided	2024-05-28	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	RCV002513551	SCV003744560	uncertain significance	Inborn genetic diseases	2021-08-17	criteria provided, single submitter	clinical testing	The c.6443C>T (p.A2148V) alteration is located in exon 29 (coding exon 29) of the ADGRV1 gene. This alteration results from a C to T substitution at nucleotide position 6443, causing the alanine (A) at amino acid position 2148 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV004737180	SCV005362376	uncertain significance	ADGRV1-related disorder	2024-09-03	no assertion criteria provided	clinical testing	The ADGRV1 c.6443C>T variant is predicted to result in the amino acid substitution p.Ala2148Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.083% of alleles in individuals of African descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.