Submissions for variant NM_032119.4(ADGRV1):c.16285G>A (p.Glu5429Lys)

gnomAD frequency: 0.00086  dbSNP: rs183851734

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000150787	SCV000198295	uncertain significance	not specified	2017-12-11	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Glu5429Lys va riant in ADGRV1 has been previously reported in 2 individuals with hearing loss by our laboratory; however, a variant affecting the remaining copy of ADGRV1 was not identified. This variant was identified in 0.24% (58/24022) of African chro mosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute .org; dbSNP rs183851734). Although this variant has been seen in the general pop ulation, its frequency is not high enough to rule out a pathogenic role. Computa tional prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, while the clinical signific ance of the p.Glu5429Lys variant is uncertain, its frequency in the general popu lation suggests that it is more likely to be benign. ACMG/AMP Criteria applied: BS1_Supporting.
Eurofins Ntd Llc (ga)	RCV000724045	SCV000232434	uncertain significance	not provided	2016-05-25	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000724045	SCV001025897	likely benign	not provided	2025-02-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000724045	SCV001795527	likely benign	not provided	2021-05-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002516028	SCV003681008	uncertain significance	Inborn genetic diseases	2021-10-20	criteria provided, single submitter	clinical testing	The c.16285G>A (p.E5429K) alteration is located in exon 76 (coding exon 76) of the ADGRV1 gene. This alteration results from a G to A substitution at nucleotide position 16285, causing the glutamic acid (E) at amino acid position 5429 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV004551309	SCV004782490	likely benign	ADGRV1-related disorder	2024-01-26	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).