Submissions for variant NM_032119.4(ADGRV1):c.6994A>T (p.Ile2332Phe)

gnomAD frequency: 0.00019  dbSNP: rs193030567

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039615	SCV000063304	likely benign	not specified	2017-04-25	criteria provided, single submitter	clinical testing	p.Ile2332Phe in exon 32 of GPR98: This variant is not expected to have clinical significance because it has been identified in 0.3% (28/10072) of Ashkenazi Jewi sh chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadin stitute.org; dbSNP rs193030567).
GeneDx	RCV000725221	SCV000168707	likely benign	not provided	2020-05-13	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26969326)
Eurofins Ntd Llc (ga)	RCV000725221	SCV000335100	uncertain significance	not provided	2015-09-11	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000725221	SCV000883364	uncertain significance	not provided	2017-12-29	criteria provided, single submitter	clinical testing	The ADGRV1 p.Ile2332Phe variant (rs193030567) was reported in one individual with a diagnosis of Usher syndrome type 2C who also harbored the p.Val617Met variant (Sloan-Heggen 2016). The p.Ile2332Phe variant is listed in the Genome Aggregation Database (gnomAD) with an allele frequency of 0.3 percent in the Ashkenazi Jewish population (identified on 28 out of 10,072 chromosomes) and has been reported to the ClinVar database (Variation ID: 46359). The isoleucine at position 2332 is highly conserved considering 12 species up to zebrafish (Alamut software v2.10.0), and computational analyses predict that this variant does affect the structure/function of the ADGRV1 protein (SIFT: damaging, MutationTaster: disease causing, PolyPhen-2: possibly damaging). Altogether, there is not enough evidence to classify the p.Ile2332Phe variant with certainty.
Mendelics	RCV000987537	SCV001136853	benign	Usher syndrome type 2C	2023-08-22	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000987537	SCV001312707	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	RCV000725221	SCV001730669	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
DECIPHERD-UDD, Universidad del Desarrollo	RCV000987537	SCV004101829	uncertain significance	Usher syndrome type 2C	2023-07-01	criteria provided, single submitter	research
CeGaT Center for Human Genetics Tuebingen	RCV000725221	SCV004159116	uncertain significance	not provided	2023-09-01	criteria provided, single submitter	clinical testing