ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.150C>G (p.Ala50=)

gnomAD frequency: 0.00070  dbSNP: rs61751580
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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000036538 SCV000060193 likely benign not specified 2010-10-05 criteria provided, single submitter clinical testing This variant has been reported in the literature in two individuals with tumors consistent with VHL syndrome. It was reported in the tumor of one individual wit h a central nervous system hemangioblastoma and in the blood of a second individ ual with a pheochromocytoma (Cybulski 2004, Meyer-Rochow 2009). However, this va riant is not expected to have clinical significance because it does not alter an amino acid residue and is not located near a splice junction. However, on rare occasions, nucleotide changes that do not result in amino acid changes can be as sociated with disease.
Invitae RCV001083936 SCV000166402 benign Chuvash polycythemia; Von Hippel-Lindau syndrome 2024-02-01 criteria provided, single submitter clinical testing
GeneDx RCV000036538 SCV000211835 benign not specified 2014-09-29 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000161100 SCV000213981 likely benign Hereditary cancer-predisposing syndrome 2014-11-12 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences RCV000679018 SCV000805321 likely benign not provided 2017-07-25 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000036538 SCV000918338 benign not specified 2018-05-07 criteria provided, single submitter clinical testing Variant summary: VHL c.150C>G alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was observed with an allele frequency of 0.0005 in 211956 control chromosomes (gnomAD). The observed variant frequency is approximately 24-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in VHL causing Von Hippel-Lindau Syndrome phenotype (2.1e-05), strongly suggesting that the variant is benign. The variant, c.150C>G, has been reported in the literature in individuals affected with Von Hippel-Lindau Syndrome (Meyer-Rochow_2008). These report(s) do not provide unequivocal conclusions about association of the variant with Von Hippel-Lindau Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Clinvar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as "benign." Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen RCV000679018 SCV001153777 likely benign not provided 2024-03-01 criteria provided, single submitter clinical testing VHL: BP4, BP7
Illumina Laboratory Services, Illumina RCV001150099 SCV001311111 benign Von Hippel-Lindau syndrome 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Sema4, Sema4 RCV000161100 SCV002534142 benign Hereditary cancer-predisposing syndrome 2021-02-03 criteria provided, single submitter curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000036538 SCV002552397 likely benign not specified 2023-08-15 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001150099 SCV004360951 benign Von Hippel-Lindau syndrome 2022-09-20 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000679018 SCV001809521 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000679018 SCV001932576 likely benign not provided no assertion criteria provided clinical testing
Clinical Genomics Labs, University Health Network RCV001150099 SCV001950148 likely benign Von Hippel-Lindau syndrome 2017-05-29 no assertion criteria provided clinical testing

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