ClinVar Miner

Submissions for variant NM_152618.3(BBS12):c.1198G>A (p.Val400Met)

gnomAD frequency: 0.00005  dbSNP: rs771136797
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000260403 SCV000332453 uncertain significance not provided 2015-06-18 criteria provided, single submitter clinical testing
Counsyl RCV000665039 SCV000789096 uncertain significance Bardet-Biedl syndrome 12 2017-01-19 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000665039 SCV001307536 uncertain significance Bardet-Biedl syndrome 12 2017-04-27 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.
Pars Genome Lab RCV000665039 SCV001736834 uncertain significance Bardet-Biedl syndrome 12 2021-05-18 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001844109 SCV002104098 uncertain significance not specified 2022-02-18 criteria provided, single submitter clinical testing Variant summary: BBS12 c.1198G>A (p.Val400Met) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 7.6e-05 in 251452 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in BBS12 causing Bardet-Biedl Syndrome (7.6e-05 vs 0.00076), allowing no conclusion about variant significance. c.1198G>A has been reported in the literature in an individual affected with Bardet-Biedl Syndrome who carried the variant in the homozygous state in cis with a different potentially pathogenic variant (Billingsley_2010). This report does not provide unequivocal conclusions about association of the variant with Bardet-Biedl Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS.
New York Genome Center RCV000665039 SCV002764583 uncertain significance Bardet-Biedl syndrome 12 2021-02-28 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000665039 SCV002814188 uncertain significance Bardet-Biedl syndrome 12 2022-01-08 criteria provided, single submitter clinical testing
Invitae RCV002519090 SCV003197853 uncertain significance Bardet-Biedl syndrome 2022-07-31 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 400 of the BBS12 protein (p.Val400Met). This variant is present in population databases (rs771136797, gnomAD 0.1%). This missense change has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 20472660). ClinVar contains an entry for this variant (Variation ID: 281597). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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