ClinVar Miner

Submissions for variant NM_001114753.3(ENG):c.1687-1G>A

dbSNP: rs1554809106
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV001806990 SCV002051685 likely pathogenic not provided 2021-01-13 criteria provided, single submitter clinical testing PVS1, PM2
Ambry Genetics RCV002397756 SCV002712564 likely pathogenic Cardiovascular phenotype 2017-04-15 criteria provided, single submitter clinical testing The c.1687-1G>A intronic variant results from a G to A substitution one nucleotide upstream from coding exon 13 of the ENG gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice acceptor site; however, direct evidence is unavailable. 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 likely pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002482336 SCV002788439 likely pathogenic Telangiectasia, hereditary hemorrhagic, type 1 2021-11-11 criteria provided, single submitter clinical testing
Invitae RCV002541392 SCV003016394 pathogenic Hereditary hemorrhagic telangiectasia 2023-10-09 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 12 of the ENG 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 ENG are known to be pathogenic (PMID: 15879500). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with hereditary hemorrhagic telangiectasia (PMID: 30701124; Invitae). ClinVar contains an entry for this variant (Variation ID: 1331646). 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.

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