Total submissions: 23
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000123108 | SCV005187298 | benign | Von Hippel-Lindau syndrome | 2024-06-25 | reviewed by expert panel | curation | The variant NM_000551.4(VHL):c.463+8C>T is an intronic variant. The GroupMax Filtering Allele Frequency (95% CI) in gnomAD v4.1.0 is 0.001101 (1359/1179388 from European, Non-Finnish Population). This is higher than the ClinGen VHL VCEP threshold of >=0.000156 (0.0156%) threshold expected for VHL disease (BA1). Therefore this variant meets the criterion for (BA1) and is classified as Benign for autosomal-dominant von Hippel-Lindau disease (VHL disease) based on the ACMG/AMP criteria applied, as specified by the ClinGen VHL VCEP Version 1.0 (Specifications approval date: 02/26/2024. Variant Approval Date 06/25/2024). |
Gene |
RCV000115747 | SCV000149656 | likely benign | not specified | 2017-11-01 | 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. |
Labcorp Genetics |
RCV001084968 | SCV000166410 | benign | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Vantari Genetics | RCV000210772 | SCV000267099 | likely benign | Hereditary cancer-predisposing syndrome | 2016-02-05 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000115747 | SCV000540656 | likely benign | not specified | 2016-03-28 | criteria provided, single submitter | clinical testing | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Outside splice consensus; 2 pubs in HGMD describe 1 proband with no segs |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589592 | SCV000697517 | benign | not provided | 2016-01-13 | criteria provided, single submitter | clinical testing | Variant summary: Variant of interest is a substitution of a non-conserved nucleotide located at an intronic position not widely known to affect splicing. 5/5 in silico tools via Alamut predict no impact on normal splicing by the variant along with mutation taster predicting a neutral outcome. The variant was found in the European and African subcohorts of the ExAC project at an allele frequency of 0.076% and 0.048% respectively. These allele frequencies exceed the maximal expected allele frequency of a disease causing VHL variant (0.0028%) indicating the variant to be non-disease causing. It was also seen in patients with phaeochromocytoma, suspected VHL disease and with sporadic RCC, however without strong evidence for pathogenicity. Multiple clinical diagnostic laboratories classify variant as Likely Benign/Benign via ClinVar (without evidence to independently evaluate). Considering the high prevalence of the variant in the general population this variant is classified as benign. |
Counsyl | RCV000123108 | SCV000785566 | likely benign | Von Hippel-Lindau syndrome | 2017-09-20 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV000589592 | SCV000805351 | likely benign | not provided | 2017-02-17 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000589592 | SCV001153780 | likely benign | not provided | 2024-03-01 | criteria provided, single submitter | clinical testing | VHL: BP4 |
Illumina Laboratory Services, |
RCV000123108 | SCV001304545 | uncertain significance | Von Hippel-Lindau syndrome | 2018-08-08 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Institute for Clinical Genetics, |
RCV000589592 | SCV002011310 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000115747 | SCV002070985 | likely benign | not specified | 2021-08-06 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000210772 | SCV002534176 | likely benign | Hereditary cancer-predisposing syndrome | 2021-02-21 | criteria provided, single submitter | curation | |
Center for Genomic Medicine, |
RCV000115747 | SCV002552404 | uncertain significance | not specified | 2024-07-31 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000210772 | SCV002636643 | benign | Hereditary cancer-predisposing syndrome | 2021-08-05 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000115747 | SCV004221483 | benign | not specified | 2023-03-30 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population (http://gnomad.broadinstitute.org) is higher than would generally be expected for pathogenic variants in this gene. Computational tools yielded predictions that this variant is unlikely to have an effect on normal RNA splicing. This nucleotide position exhibits low evolutionary conservation. |
Genomic Diagnostic Laboratory, |
RCV000123108 | SCV000264746 | likely benign | Von Hippel-Lindau syndrome | 2016-02-26 | no assertion criteria provided | clinical testing | |
Diagnostic Laboratory, |
RCV000589592 | SCV001741627 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000589592 | SCV001808973 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000589592 | SCV001930615 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genomics Labs, |
RCV000123108 | SCV001950149 | likely benign | Von Hippel-Lindau syndrome | 2018-11-22 | no assertion criteria provided | clinical testing | |
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000589592 | SCV001956241 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000589592 | SCV001968532 | likely benign | not provided | no assertion criteria provided | clinical testing |