ClinVar Miner

Submissions for variant NM_004329.3(BMPR1A):c.430+1G>A

dbSNP: rs1843283551
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001036622 SCV001199995 pathogenic Juvenile polyposis syndrome 2024-03-13 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 6 of the BMPR1A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BMPR1A are known to be pathogenic (PMID: 11536076, 12417513). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with juvenile polyposis syndrome (Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 835681). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002327250 SCV002626745 pathogenic Hereditary cancer-predisposing syndrome 2022-02-27 criteria provided, single submitter clinical testing The c.430+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 4 of the BMPR1A gene. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In silico splice site analysis predicts that this alteration will weaken the native splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.

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