ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.1059A>G (p.Gln353=) (rs1060503407)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000459865 SCV000552890 uncertain significance Juvenile polyposis syndrome 2018-10-07 criteria provided, single submitter clinical testing This sequence change affects codon 353 of the BMPR1A mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the BMPR1A protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BMPR1A-related disease. ClinVar contains an entry for this variant (Variation ID: 411640). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Ambry Genetics RCV000571926 SCV000668325 likely benign Hereditary cancer-predisposing syndrome 2016-04-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign
Integrated Genetics/Laboratory Corporation of America RCV000614387 SCV000698306 uncertain significance not specified 2019-08-21 criteria provided, single submitter clinical testing Variant summary: BMPR1A c.1059A>G alters a conserved nucleotide resulting in a synonymous change. Several computational tools via ALAMUT predict a significant impact on normal splicing: Two predict the variant creates a cryptic exonic 3' acceptor site. Two predict the variant to have no significant impact on splicing. Another in-silico tool for assessing the pathogenicity of synonymous variants, namely TraP (Transcript-inferred Pathogenicity, Gelfman_2017) predicts this variant to be possibly pathogenic. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-06 in 250796 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1059A>G in individuals affected with Juvenile Polyposis Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (three as likely benign and one as uncertain significance). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
GeneDx RCV000614387 SCV000726066 likely benign not specified 2017-12-19 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.
Counsyl RCV000459865 SCV000786463 likely benign Juvenile polyposis syndrome 2018-05-08 criteria provided, single submitter clinical testing

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