ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1859_1860insAT (p.Phe620fs)

dbSNP: rs756358866
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001956423 SCV002238466 pathogenic Hereditary nonpolyposis colorectal neoplasms 2023-11-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe620Leufs*4) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). This variant is present in population databases (rs756358866, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with testicular germ cell tumor (PMID: 30676620). ClinVar contains an entry for this variant (Variation ID: 1458544). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002407188 SCV002721882 pathogenic Hereditary cancer-predisposing syndrome 2021-11-24 criteria provided, single submitter clinical testing The c.1859_1860insAT pathogenic mutation, located in coding exon 11 of the PMS2 gene, results from an insertion of two nucleotides at position 1859, causing a translational frameshift with a predicted alternate stop codon (p.F620Lfs*4). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc. RCV003453882 SCV004188584 pathogenic Lynch syndrome 4 2023-09-21 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Baylor Genetics RCV003453882 SCV004205381 likely pathogenic Lynch syndrome 4 2023-10-16 criteria provided, single submitter clinical testing

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