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NM_000535.7(PMS2):c.251-1G>C AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 4, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003759864.2

Allele description [Variation Report for NM_000535.7(PMS2):c.251-1G>C]

NM_000535.7(PMS2):c.251-1G>C

Gene:
PMS2:PMS1 homolog 2, mismatch repair system component [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p22.1
Genomic location:
Preferred name:
NM_000535.7(PMS2):c.251-1G>C
HGVS:
  • NC_000007.14:g.6003793C>G
  • NG_008466.1:g.10314G>C
  • NM_000535.5:c.251-1G>C
  • NM_000535.7:c.251-1G>CMANE SELECT
  • NM_001322003.2:c.-155-1G>C
  • NM_001322004.2:c.-155-1G>C
  • NM_001322005.2:c.-155-1G>C
  • NM_001322006.2:c.251-1G>C
  • NM_001322007.2:c.35+179G>C
  • NM_001322008.2:c.35+179G>C
  • NM_001322009.2:c.-155-1G>C
  • NM_001322010.2:c.-155-1G>C
  • NM_001322011.2:c.-634-1G>C
  • NM_001322012.2:c.-634-1G>C
  • NM_001322013.2:c.-155-1G>C
  • NM_001322014.2:c.251-1G>C
  • NM_001322015.2:c.-234-1G>C
  • NM_001406866.1:c.437-1G>C
  • NM_001406868.1:c.274G>C
  • NM_001406869.1:c.251-1G>C
  • NM_001406870.1:c.251-1G>C
  • NM_001406871.1:c.251-1G>C
  • NM_001406872.1:c.251-1G>C
  • NM_001406873.1:c.251-1G>C
  • NM_001406874.1:c.251-1G>C
  • NM_001406875.1:c.-234-1G>C
  • NM_001406876.1:c.35+179G>C
  • NM_001406877.1:c.-234-1G>C
  • NM_001406878.1:c.-234-1G>C
  • NM_001406879.1:c.-234-1G>C
  • NM_001406880.1:c.-181-1G>C
  • NM_001406881.1:c.-132+179G>C
  • NM_001406882.1:c.-234-1G>C
  • NM_001406883.1:c.35+179G>C
  • NM_001406884.1:c.251-1G>C
  • NM_001406885.1:c.250+179G>C
  • NM_001406886.1:c.251-1G>C
  • NM_001406887.1:c.-155-1G>C
  • NM_001406888.1:c.-102-1G>C
  • NM_001406889.1:c.-102-1G>C
  • NM_001406890.1:c.-145-1G>C
  • NM_001406891.1:c.-155-1G>C
  • NM_001406892.1:c.-102-1G>C
  • NM_001406893.1:c.-155-1G>C
  • NM_001406894.1:c.-102-1G>C
  • NM_001406895.1:c.-102-1G>C
  • NM_001406896.1:c.-52-1157G>C
  • NM_001406897.1:c.-155-1G>C
  • NM_001406898.1:c.-155-1G>C
  • NM_001406899.1:c.-102-1G>C
  • NM_001406900.1:c.-132+179G>C
  • NM_001406901.1:c.35+179G>C
  • NM_001406902.1:c.35+179G>C
  • NM_001406903.1:c.35+179G>C
  • NM_001406904.1:c.-102-1G>C
  • NM_001406905.1:c.-155-1G>C
  • NM_001406906.1:c.-155-1G>C
  • NM_001406907.1:c.-102-1G>C
  • NM_001406908.1:c.-155-1G>C
  • NM_001406909.1:c.-102-1G>C
  • NM_001406910.1:c.-155-1G>C
  • NM_001406911.1:c.-155-1G>C
  • NM_001406912.1:c.251-1G>C
  • NP_001393797.1:p.Ala92Pro
  • LRG_161t1:c.251-1G>C
  • LRG_161:g.10314G>C
  • NC_000007.13:g.6043424C>G
Protein change:
A92P
Molecular consequence:
  • NM_001322007.2:c.35+179G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322008.2:c.35+179G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406876.1:c.35+179G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406881.1:c.-132+179G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406883.1:c.35+179G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406885.1:c.250+179G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406896.1:c.-52-1157G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406900.1:c.-132+179G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406901.1:c.35+179G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406902.1:c.35+179G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406903.1:c.35+179G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406868.1:c.274G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000535.7:c.251-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322003.2:c.-155-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322004.2:c.-155-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322005.2:c.-155-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322006.2:c.251-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322009.2:c.-155-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322010.2:c.-155-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322011.2:c.-634-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322012.2:c.-634-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322013.2:c.-155-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322014.2:c.251-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322015.2:c.-234-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406866.1:c.437-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406869.1:c.251-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406870.1:c.251-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406871.1:c.251-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406872.1:c.251-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406873.1:c.251-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406874.1:c.251-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406875.1:c.-234-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406877.1:c.-234-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406878.1:c.-234-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406879.1:c.-234-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406880.1:c.-181-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406882.1:c.-234-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406884.1:c.251-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406886.1:c.251-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406887.1:c.-155-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406888.1:c.-102-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406889.1:c.-102-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406890.1:c.-145-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406891.1:c.-155-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406892.1:c.-102-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406893.1:c.-155-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406894.1:c.-102-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406895.1:c.-102-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406897.1:c.-155-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406898.1:c.-155-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406899.1:c.-102-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406904.1:c.-102-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406905.1:c.-155-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406906.1:c.-155-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406907.1:c.-102-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406908.1:c.-155-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406909.1:c.-102-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406910.1:c.-155-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406911.1:c.-155-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406912.1:c.251-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Hereditary nonpolyposis colorectal neoplasms
Identifiers:
MeSH: D003123; MedGen: C0009405

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004376155Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Mar 4, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations.

Senter L, Clendenning M, Sotamaa K, Hampel H, Green J, Potter JD, Lindblom A, Lagerstedt K, Thibodeau SN, Lindor NM, Young J, Winship I, Dowty JG, White DM, Hopper JL, Baglietto L, Jenkins MA, de la Chapelle A.

Gastroenterology. 2008 Aug;135(2):419-28. doi: 10.1053/j.gastro.2008.04.026. Epub 2008 May 2.

PubMed [citation]
PMID:
18602922
PMCID:
PMC2759321

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004376155.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change affects an acceptor splice site in intron 3 of the PMS2 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in skipping of exon 4 and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. Disruption of this splice site has been observed in individuals with Lynch syndrome (PMID: 18602922; Invitae). This variant is present in population databases (rs764171734, gnomAD 0.003%).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024