ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.956dup (p.Asn319fs)

dbSNP: rs752179149
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414704 SCV000490542 pathogenic not provided 2021-11-10 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 25412400, 26969326, 31589614)
Blueprint Genetics RCV001074761 SCV001240356 pathogenic Retinal dystrophy 2019-05-27 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000414704 SCV001416907 pathogenic not provided 2024-01-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn319Lysfs*6) in the ADGRV1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ADGRV1 are known to be pathogenic (PMID: 19357117, 22135276, 22147658, 26226137, 30718709, 31047384, 32467589). This variant is present in population databases (rs752179149, gnomAD 0.002%). This premature translational stop signal has been observed in individuals with Usher syndrome (PMID: 25412400, 26969326). ClinVar contains an entry for this variant (Variation ID: 372373). For these reasons, this variant has been classified as Pathogenic.
INGEBI, INGEBI / CONICET RCV001544532 SCV001763578 pathogenic Usher syndrome type 2C 2021-07-15 criteria provided, single submitter clinical testing Based on ACMG/AMP guidelines and Hearing Loss Expert Panel specific criteria:The c.956dup variant in ADGRV1 gene is predicted to cause a premature stop codon in biologically-relevant-exon 7/90 that leads to a truncated or absent protein in a gene in which loss-of-function is an established mechanism, NMD is predcited to occur, (PVS1). The variant is only present in european non-finnsih population (3/128336 alleles, 0.0006% with 95% CI) meeting PM2. The c.956 dup A variant has been identified in trans with a pathogenic variant a patient with Usher Syndrome. Besides, the proband have two unaffected siblings wich only carried this variant (this report) PM3, PP1_Sup, PP4. There is another report in which c.956 dup variant was detect in trans with a VUS, hence this evidence was not counted (PMID: 26969326). Taking all the information together together :PVS1, PM2, PM3, PP1_Sup, PP4, c.956dup A is classified as Pathogenic for Usher Syndrome.
Fulgent Genetics, Fulgent Genetics RCV005033936 SCV005666273 pathogenic Usher syndrome type 2C; Febrile seizures, familial, 4 2024-04-03 criteria provided, single submitter clinical testing

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