ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.142del (p.Asp48fs) (rs1064794173)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478389 SCV000568066 pathogenic not provided 2018-07-10 criteria provided, single submitter clinical testing This deletion of one nucleotide in PMS2 is denoted c.142delG at the cDNA level and p.Asp48MetfsX9 (D48MfsX9) at the protein level. The normal sequence, with the base that is deleted in brackets, is TCTG[delG]ATGC. The deletion causes a frameshift, which changes an Aspartic Acid to a Methionine at codon 48, and creates a premature stop codon at position 9 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. PMS2 c.142delG has been reported in at least one individual with colorectal cancer (Roberts 2018). Based on currently available evidence, we consider this variant to be pathogenic.
Invitae RCV000800178 SCV000939878 pathogenic Hereditary nonpolyposis colon cancer 2018-08-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asp48Metfs*9) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 419888). 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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