Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene label mismatch: PMS2 vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000535.7(PMS2):c.1571dup (p.Gly525fs)

CA658655976

480313 (ClinVar)

Gene: PMS2
Condition: colorectal cancer, hereditary nonpolyposis, type 4
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 40ecbd71-73d6-469f-8b66-881aa93b2d90
Approved on: 2025-03-13
Published on: 2025-03-20

HGVS expressions

NM_000535.7:c.1571dup
NM_000535.7(PMS2):c.1571dup (p.Gly525fs)
NC_000007.14:g.5987197dup
CM000669.2:g.5987197dup
NC_000007.13:g.6026828dup
CM000669.1:g.6026828dup
NC_000007.12:g.5993354dup
NG_008466.1:g.26913dup
ENST00000699814.2:c.*967dup
ENST00000699840.2:c.1568dup
ENST00000699930.2:c.1463dup
ENST00000406569.8:c.1571dup
ENST00000644110.2:c.*1165dup
ENST00000699752.1:c.1415dup
ENST00000699753.1:c.*992dup
ENST00000699754.1:c.1373dup
ENST00000699755.1:c.*970dup
ENST00000699756.1:c.*1158dup
ENST00000699757.1:c.*828dup
ENST00000699758.1:c.*828dup
ENST00000699759.1:n.2425dup
ENST00000699760.1:c.1253dup
ENST00000699761.1:c.1166dup
ENST00000699762.1:c.998dup
ENST00000699763.1:c.*661dup
ENST00000699764.1:c.1553+18dup
ENST00000699765.1:c.*667dup
ENST00000699766.1:c.1571dup
ENST00000699767.1:c.1571dup
ENST00000699768.1:c.1571dup
ENST00000699811.1:c.1166dup
ENST00000699813.1:n.1684dup
ENST00000699814.1:c.1194dup
ENST00000699815.1:c.*1102dup
ENST00000699816.1:c.*461dup
ENST00000699817.1:c.*1165dup
ENST00000699818.1:c.1166dup
ENST00000699819.1:c.*728dup
ENST00000699820.1:c.1144+2606dup
ENST00000699821.1:c.1166dup
ENST00000699822.1:c.*1023dup
ENST00000699823.1:c.1166dup
ENST00000699824.1:c.*1074dup
ENST00000699825.1:c.1010dup
ENST00000699826.1:c.*970dup
ENST00000699827.1:c.1403dup
ENST00000699828.1:c.*661dup
ENST00000699833.1:n.3343dup
ENST00000699837.1:c.1166dup
ENST00000699838.1:c.*1471dup
ENST00000699839.1:c.1757dup
ENST00000699916.1:c.*828dup
ENST00000699917.1:c.*1020dup
ENST00000699918.1:c.*1072dup
ENST00000699919.1:c.*1158dup
ENST00000699920.1:c.*1207dup
ENST00000699928.1:c.989-4203dup
ENST00000699929.1:c.*872dup
ENST00000699930.1:c.1463dup
ENST00000699931.1:n.2999dup
ENST00000699951.1:c.*667dup
ENST00000699952.1:c.803+10132dup
ENST00000699953.1:c.*678dup
ENST00000699954.1:c.*872dup
ENST00000265849.12:c.1571dup
ENST00000642292.1:c.1166dup
ENST00000642456.1:c.1166dup
ENST00000643595.1:c.*970dup
ENST00000644110.1:c.1253dup
ENST00000265849.11:c.1571dup
ENST00000382321.5:c.804-4203dup
ENST00000406569.7:n.1571dup
ENST00000441476.6:c.1253dup
ENST00000469652.1:n.63-4289dup
NM_000535.5:c.1571dup
NR_003085.2:n.1653dup
NM_000535.6:c.1571dup
NM_001322003.1:c.1166dup
NM_001322004.1:c.1166dup
NM_001322005.1:c.1166dup
NM_001322006.1:c.1415dup
NM_001322007.1:c.1253dup
NM_001322008.1:c.1253dup
NM_001322009.1:c.1166dup
NM_001322010.1:c.1010dup
NM_001322011.1:c.638dup
NM_001322012.1:c.638dup
NM_001322013.1:c.998dup
NM_001322014.1:c.1571dup
NM_001322015.1:c.1262dup
NR_136154.1:n.1658dup
NM_001322003.2:c.1166dup
NM_001322004.2:c.1166dup
NM_001322005.2:c.1166dup
NM_001322006.2:c.1415dup
NM_001322008.2:c.1253dup
NM_001322009.2:c.1166dup
NM_001322010.2:c.1010dup
NM_001322011.2:c.638dup
NM_001322012.2:c.638dup
NM_001322013.2:c.998dup
NM_001322014.2:c.1571dup
NM_001322015.2:c.1262dup
NM_001322007.2:c.1253dup
More

Pathogenic

Met criteria codes 3
PVS1 PM2_Supporting PM3_Supporting

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PMS2 Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP
The c.1571dup (p.Gly525ArgfsTer17) (NM_000535.7) variant in PMS2 is a frameshift variant located between codon 525 and 542 and predicted to cause a premature stop codon in exon 11 in a gene in which loss-of-function is an established disease mechanism (PVS1). This alteration was detected in homozygous state (PMID: 26391938) in an individual meeting the clinical criteria for CMMR-D (≥3 points, table 3 of the ClinGen_InSiGHTColorectalCancer/Polyposis_ACMG_Specifications_v1), (PM3_supporting met). This variant is absent from gnomAD v2.1.1 and gnomAD v4.1 (PM2_supporting). In summary, this variant meets the criteria to be classified as pathogenic for Lynch-Syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/ Polyposis VCEP: PVS1, PM2_SUP, PM3_SUP (VCEP specifications version 1)
Met criteria codes
PVS1
The c.1571dup (p.Gly525ArgfsTer17) (NM_000535.7) variant in PMS2 is a frameshift variant located between codon 525 and 542 and predicted to cause a premature stop codon in exon 11 in a gene in which loss-of-function is an established disease mechanism (PVS1).
PM2_Supporting
This variant is absent from gnomAD v2.1.1 and gnomAD v4.1 (PM2_supporting).
PM3_Supporting
This alteration was detected in homozygous state in an individual meeting the clinical criteria for CMMR-D (≥3 points, table 3 of the ClinGen_InSiGHTColorectalCancer/Polyposis_ACMG_Specifications_v1), (PM3_supporting met).
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.