ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.150C>G (p.Ala50=) (rs61751580)

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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 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 RCV000679018 SCV000166402 benign not provided 2019-03-05 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
PreventionGenetics,PreventionGenetics RCV000679018 SCV000805321 likely benign not provided 2017-07-25 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America 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.

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