Submissions for variant NM_032119.4(ADGRV1):c.8110A>T (p.Ile2704Phe)

gnomAD frequency: 0.00005  dbSNP: rs376318779

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039639	SCV000063328	uncertain significance	not specified	2018-11-28	criteria provided, single submitter	clinical testing	The p.Ile2704Phe variant in GPR98 has been previously reported by our laboratory in 5 individuals with hearing loss; however none of them carried a second varia nt affecting the remaining copy of GPR98. In addition, three of them had pathoge nic variants in a different gene that explain their hearing loss. The variant ha s also been identified in 0.02% (8/35350) of Latino chromosomes and 0.02% (27/12 8098) of European chromosomes by the Genome Aggregation Database (gnomAD, http:/ /gnomad.broadinstitute.org). This variant has been reported in ClinVar (Variatio n ID 46383). Computational prediction tools and conservation analysis do not pro vide strong support for or against an impact to the protein. In summary, the cl inical significance of the p.Ile2704Phe variant is uncertain. ACMG/AMP Criteria: none.
Eurofins Ntd Llc (ga)	RCV000727071	SCV000705377	uncertain significance	not provided	2017-01-23	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000765845	SCV000897241	uncertain significance	Usher syndrome type 2C; Febrile seizures, familial, 4	2018-10-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000727071	SCV001154442	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	ADGRV1: BP4
Illumina Laboratory Services, Illumina	RCV001151659	SCV001312824	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000727071	SCV001414924	likely benign	not provided	2024-12-12	criteria provided, single submitter	clinical testing
Department of Otolaryngology – Head & Neck Surgery, Cochlear Implant Center	RCV001375445	SCV001572070	uncertain significance	Hearing impairment	2021-04-12	criteria provided, single submitter	clinical testing	PM2_Supporting, BP4_Supporting
GeneDx	RCV000727071	SCV001773399	uncertain significance	not provided	2022-11-02	criteria provided, single submitter	clinical testing	Reported in a patient with blindness in published literature (Dieiro et al., 2020); clinical and molecular information is limited; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32483926)