ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.15608A>G (p.Glu5203Gly) (rs202106463)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000039536 SCV000063225 benign not specified 2015-06-02 criteria provided, single submitter clinical testing Glu5203Gly in exon 74 of GPR98: This variant is not expected to have clinical si gnificance because it has been identified in 0.7% (85/11574) of Latino chromosom es, including 3 homozygotes, by the Exome Aggregation Consortium (ExAC, http://e; dbSNP rs202106463).
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000724510 SCV000232420 uncertain significance not provided 2014-12-23 criteria provided, single submitter clinical testing
GeneDx RCV000724510 SCV000969533 likely benign not provided 2020-10-26 criteria provided, single submitter clinical testing
Invitae RCV000724510 SCV001024546 benign not provided 2020-11-03 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001155929 SCV001317396 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.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000724510 SCV001549504 likely benign not provided no assertion criteria provided clinical testing The ADGRV1 p.Glu5203Gly variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs202106463) and in ClinVar (classified as a VUS by EGL Genetic Diagnostics and as benign by Laboratory for Molecular Medicine). The variant was identified in control databases in 265 of 280608 chromosomes (1 homozygous) at a frequency of 0.000944 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Other in 32 of 7142 chromosomes (freq: 0.004481), Ashkenazi Jewish in 45 of 10352 chromosomes (freq: 0.004347), Latino in 140 of 35374 chromosomes (freq: 0.003958), European (non-Finnish) in 41 of 128386 chromosomes (freq: 0.000319), South Asian in 6 of 30602 chromosomes (freq: 0.000196) and African in 1 of 24192 chromosomes (freq: 0.000041); it was not observed in the East Asian or European (Finnish) populations. The p.Glu5203Gly residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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