ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1731_1732delinsAGT (p.Arg578fs) (rs1057515572)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000657177 SCV000778898 pathogenic not provided 2016-12-01 criteria provided, single submitter clinical testing This combined deletion and insertion is denoted PMS2 c.1731_1732delGCinsAGT at the cDNA level and p.Arg578ValfsX3 (R578VfsX3) at the protein level. The surrounding sequence is CAAA[delGC][insAGT]GTTT. The variant causes a frameshift which changes an Arginine to a Valine at codon 578, and creates a premature stop codon at position 3 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.1731_1732delGCinsAGT, also reported as the combined variants PMS2 c.1730_1731insA and c.1732C>T, has been detected in trans with a second pathogenic PMS2 variant in two siblings with constitutional mismatch repair deficiency syndrome (CMMR-D, Auclair 2007). We consider this variant to be pathogenic.
Geisinger Autism and Developmental Medicine Institute,Geisinger Health System RCV000678287 SCV000804344 likely pathogenic Hereditary nonpolyposis colorectal cancer type 4 2018-02-20 criteria provided, single submitter provider interpretation This 14 year old male has a history of intellectual disability, macrocephaly, overgrowth, and hyperinsulinemia. Genetic testing to date, including exome sequencing, has not yielded a diagnosis, but did identify a secondary finding. This variant was reported previously in a compound heterozygous state in siblings with early only cancer and a family history of colon cancer (Auclair, 2007). It is absent from gnomAD. It is expected to cause a frameshift resulting in a premature stop codon. There is no reported paternal family history of cancer.
Ambry Genetics RCV001012887 SCV001173401 pathogenic Hereditary cancer-predisposing syndrome 2019-04-11 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Color RCV001012887 SCV001343306 pathogenic Hereditary cancer-predisposing syndrome 2020-02-04 criteria provided, single submitter clinical testing
OMIM RCV000009825 SCV000030046 pathogenic Turcot syndrome 2007-11-01 no assertion criteria provided literature only

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