ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.2156del (p.Gln719fs) (rs786201062)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162471 SCV000212835 pathogenic Hereditary cancer-predisposing syndrome 2017-04-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000482434 SCV000565837 pathogenic not provided 2017-01-19 criteria provided, single submitter clinical testing This deletion of one nucleotide in PMS2 is denoted c.2156delA at the cDNA level and p.Gln719ArgfsX6 (Q719RfsX6) at the protein level. The normal sequence, with the base that is deleted in brackets, is CTCC[delA]GGGGC. The deletion causes a frameshift, which changes a Glutamine to an Arginine at codon 719, and creates a premature stop codon at position 6 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.2156delA has been reported in association with Lynch syndrome (Suerink 2015). We consider this variant to be pathogenic.
Invitae RCV000547624 SCV000625584 pathogenic Hereditary nonpolyposis colon cancer 2018-09-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln719Argfs*6) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases (rs786201062, ExAC) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This variant has been reported in a family with Lynch syndrome (PMID: 26110232). ClinVar contains an entry for this variant (Variation ID: 183755). Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics RCV000482434 SCV000806200 pathogenic not provided 2017-05-26 criteria provided, single submitter clinical testing

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