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NM_000535.7(PMS2):c.251-2A>T AND Hereditary nonpolyposis colon cancer

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 22, 2020
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:
RCV001255210.1

Allele description [Variation Report for NM_000535.7(PMS2):c.251-2A>T]

NM_000535.7(PMS2):c.251-2A>T

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.251-2A>T
HGVS:
  • NC_000007.14:g.6003794T>A
  • NG_008466.1:g.10313A>T
  • NM_000535.7:c.251-2A>TMANE SELECT
  • NM_001322003.2:c.-155-2A>T
  • NM_001322004.2:c.-155-2A>T
  • NM_001322005.2:c.-155-2A>T
  • NM_001322006.2:c.251-2A>T
  • NM_001322007.2:c.35+178A>T
  • NM_001322008.2:c.35+178A>T
  • NM_001322009.2:c.-155-2A>T
  • NM_001322010.2:c.-155-2A>T
  • NM_001322011.2:c.-634-2A>T
  • NM_001322012.2:c.-634-2A>T
  • NM_001322013.2:c.-155-2A>T
  • NM_001322014.2:c.251-2A>T
  • NM_001322015.2:c.-234-2A>T
  • NM_001406866.1:c.437-2A>T
  • NM_001406868.1:c.273A>T
  • NM_001406869.1:c.251-2A>T
  • NM_001406870.1:c.251-2A>T
  • NM_001406871.1:c.251-2A>T
  • NM_001406872.1:c.251-2A>T
  • NM_001406873.1:c.251-2A>T
  • NM_001406874.1:c.251-2A>T
  • NM_001406875.1:c.-234-2A>T
  • NM_001406876.1:c.35+178A>T
  • NM_001406877.1:c.-234-2A>T
  • NM_001406878.1:c.-234-2A>T
  • NM_001406879.1:c.-234-2A>T
  • NM_001406880.1:c.-181-2A>T
  • NM_001406881.1:c.-132+178A>T
  • NM_001406882.1:c.-234-2A>T
  • NM_001406883.1:c.35+178A>T
  • NM_001406884.1:c.251-2A>T
  • NM_001406885.1:c.250+178A>T
  • NM_001406886.1:c.251-2A>T
  • NM_001406887.1:c.-155-2A>T
  • NM_001406888.1:c.-102-2A>T
  • NM_001406889.1:c.-102-2A>T
  • NM_001406890.1:c.-145-2A>T
  • NM_001406891.1:c.-155-2A>T
  • NM_001406892.1:c.-102-2A>T
  • NM_001406893.1:c.-155-2A>T
  • NM_001406894.1:c.-102-2A>T
  • NM_001406895.1:c.-102-2A>T
  • NM_001406896.1:c.-52-1158A>T
  • NM_001406897.1:c.-155-2A>T
  • NM_001406898.1:c.-155-2A>T
  • NM_001406899.1:c.-102-2A>T
  • NM_001406900.1:c.-132+178A>T
  • NM_001406901.1:c.35+178A>T
  • NM_001406902.1:c.35+178A>T
  • NM_001406903.1:c.35+178A>T
  • NM_001406904.1:c.-102-2A>T
  • NM_001406905.1:c.-155-2A>T
  • NM_001406906.1:c.-155-2A>T
  • NM_001406907.1:c.-102-2A>T
  • NM_001406908.1:c.-155-2A>T
  • NM_001406909.1:c.-102-2A>T
  • NM_001406910.1:c.-155-2A>T
  • NM_001406911.1:c.-155-2A>T
  • NM_001406912.1:c.251-2A>T
  • NP_001393797.1:p.Ser91=
  • LRG_161t1:c.251-2A>T
  • LRG_161:g.10313A>T
  • NC_000007.13:g.6043425T>A
  • NM_000535.5:c.251-2A>T
  • NM_000535.6:c.251-2A>T
Links:
dbSNP: rs587779340
NCBI 1000 Genomes Browser:
rs587779340
Molecular consequence:
  • NM_001322007.2:c.35+178A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322008.2:c.35+178A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406876.1:c.35+178A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406881.1:c.-132+178A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406883.1:c.35+178A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406885.1:c.250+178A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406896.1:c.-52-1158A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406900.1:c.-132+178A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406901.1:c.35+178A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406902.1:c.35+178A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406903.1:c.35+178A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000535.7:c.251-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322003.2:c.-155-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322004.2:c.-155-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322005.2:c.-155-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322006.2:c.251-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322009.2:c.-155-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322010.2:c.-155-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322011.2:c.-634-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322012.2:c.-634-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322013.2:c.-155-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322014.2:c.251-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322015.2:c.-234-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406866.1:c.437-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406869.1:c.251-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406870.1:c.251-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406871.1:c.251-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406872.1:c.251-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406873.1:c.251-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406874.1:c.251-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406875.1:c.-234-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406877.1:c.-234-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406878.1:c.-234-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406879.1:c.-234-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406880.1:c.-181-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406882.1:c.-234-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406884.1:c.251-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406886.1:c.251-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406887.1:c.-155-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406888.1:c.-102-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406889.1:c.-102-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406890.1:c.-145-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406891.1:c.-155-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406892.1:c.-102-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406893.1:c.-155-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406894.1:c.-102-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406895.1:c.-102-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406897.1:c.-155-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406898.1:c.-155-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406899.1:c.-102-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406904.1:c.-102-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406905.1:c.-155-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406906.1:c.-155-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406907.1:c.-102-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406908.1:c.-155-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406909.1:c.-102-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406910.1:c.-155-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406911.1:c.-155-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406912.1:c.251-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406868.1:c.273A>T - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:
Hereditary nonpolyposis colon cancer (HNPCC)
Synonyms:
Hereditary nonpolyposis colorectal cancer; Familial nonpolyposis colon cancer; Hereditary Nonpolyposis Colorectal Cancer Syndrome
Identifiers:
MONDO: MONDO:0018630; MedGen: C1333990; OMIM: PS120435

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000920018Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Jun 22, 2020) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome.

Yurgelun MB, Allen B, Kaldate RR, Bowles KR, Judkins T, Kaushik P, Roa BB, Wenstrup RJ, Hartman AR, Syngal S.

Gastroenterology. 2015 Sep;149(3):604-13.e20. doi: 10.1053/j.gastro.2015.05.006. Epub 2015 May 14.

PubMed [citation]
PMID:
25980754
PMCID:
PMC4550537

Improving performance of multigene panels for genomic analysis of cancer predisposition.

Shirts BH, Casadei S, Jacobson AL, Lee MK, Gulsuner S, Bennett RL, Miller M, Hall SA, Hampel H, Hisama FM, Naylor LV, Goetsch C, Leppig K, Tait JF, Scroggins SM, Turner EH, Livingston R, Salipante SJ, King MC, Walsh T, Pritchard CC.

Genet Med. 2016 Oct;18(10):974-81. doi: 10.1038/gim.2015.212. Epub 2016 Feb 4.

PubMed [citation]
PMID:
26845104
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000920018.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: PMS2 c.251-2A>T is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.1e-06 in 244282 control chromosomes (gnomAD). c.251-2A>T has been reported in the literature in individuals affected with Hereditary Nonpolyposis Colorectal Cancer (e.g. Yurgelun_2015). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight ClinVar submitters (evaluation after 2014) cite the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Oct 8, 2024