ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.583C>A (p.Gln195Lys) (rs771910503)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000206242 SCV000260768 uncertain significance Juvenile polyposis syndrome 2017-11-08 criteria provided, single submitter clinical testing This sequence change replaces glutamine with lysine at codon 195 of the BMPR1A protein (p.Gln195Lys). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and lysine. This variant is present in population databases (rs771910503, ExAC 0.02%). This variant has not been reported in the literature in individuals with BMPR1A-related disease. ClinVar contains an entry for this variant (Variation ID: 220316). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Integrated Genetics/Laboratory Corporation of America RCV000586948 SCV000698317 uncertain significance not provided 2016-08-01 criteria provided, single submitter clinical testing Variant summary: The BMPR1A c.583C>A (p.Gln195Lys) variant causes a missense change involving a conserved nucleotide with 3/4 in silico tools (SNPs&GO not captured due to low reliability index) predict a benign outcome, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 2/121234 (1/60617), predominantly in the African cohort, 2/10390 (1/5194), which is approximately 8 times the estimated maximal expected allele frequency for a pathogenic BMPR1A variant of 1/500000. Therefore, suggesting that the variant could be a rare polymorphism found in population(s) of African origin. However, this observation needs to be cautiously considered due to ExAC harboring individuals that could have a BMPR1A phenotype. The variant of interest has not been reported in affected individuals via publications, to our knowledge. A clinical laboratory cites the variant as "uncertain significance. Therefore, until additional information becomes available (ie, clinical and functional studies), the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)."

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