ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1576del (p.Asp526fs) (rs863224497)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000216824 SCV000279876 pathogenic not provided 2016-02-04 criteria provided, single submitter clinical testing This deletion of one nucleotide in PMS2 is denoted c.1576delG at the cDNA level and p.Asp526ThrfsX69 (D526TfsX69) at the protein level. The normal sequence, with the base that is deleted in braces, is AGGG[G]ACAG. The deletion causes a frameshift, which changes an Aspartic Acid to a Threonine at codon 526, and creates a premature stop codon at position 69 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Invitae RCV000199929 SCV000253844 pathogenic Lynch syndrome 2016-09-12 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 11 of the PMS2 mRNA (c.1576delG), causing a frameshift at codon 526. This creates a premature translational stop signal (p.Asp526Thrfs*69) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). For these reasons, this variant has been classified as Pathogenic.

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