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NM_000535.7(PMS2):c.2007-2A>C AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 26, 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:
RCV000818298.9

Allele description [Variation Report for NM_000535.7(PMS2):c.2007-2A>C]

NM_000535.7(PMS2):c.2007-2A>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.2007-2A>C
HGVS:
  • NC_000007.14:g.5982993T>G
  • NG_008466.1:g.31114A>C
  • NM_000535.7:c.2007-2A>CMANE SELECT
  • NM_001322003.2:c.1602-2A>C
  • NM_001322004.2:c.1602-2A>C
  • NM_001322005.2:c.1602-2A>C
  • NM_001322006.2:c.1851-2A>C
  • NM_001322007.2:c.1689-2A>C
  • NM_001322008.2:c.1689-2A>C
  • NM_001322009.2:c.1602-2A>C
  • NM_001322010.2:c.1446-2A>C
  • NM_001322011.2:c.1074-2A>C
  • NM_001322012.2:c.1074-2A>C
  • NM_001322013.2:c.1434-2A>C
  • NM_001322014.2:c.2007-2A>C
  • NM_001322015.2:c.1698-2A>C
  • NM_001406866.1:c.2193-2A>C
  • NM_001406868.1:c.2031-2A>C
  • NM_001406869.1:c.1899-2A>C
  • NM_001406870.1:c.1851-2A>C
  • NM_001406871.1:c.2007-2A>C
  • NM_001406872.1:c.2006+3766A>C
  • NM_001406873.1:c.1809-2A>C
  • NM_001406874.1:c.1839-2A>C
  • NM_001406875.1:c.1698-2A>C
  • NM_001406876.1:c.1689-2A>C
  • NM_001406877.1:c.1698-2A>C
  • NM_001406878.1:c.1698-2A>C
  • NM_001406879.1:c.1698-2A>C
  • NM_001406880.1:c.1698-2A>C
  • NM_001406881.1:c.1698-2A>C
  • NM_001406882.1:c.1698-2A>C
  • NM_001406883.1:c.1689-2A>C
  • NM_001406884.1:c.1683-2A>C
  • NM_001406885.1:c.1671-2A>C
  • NM_001406886.1:c.1641-2A>C
  • NM_001406887.1:c.1602-2A>C
  • NM_001406888.1:c.1602-2A>C
  • NM_001406889.1:c.1602-2A>C
  • NM_001406890.1:c.1602-2A>C
  • NM_001406891.1:c.1602-2A>C
  • NM_001406892.1:c.1602-2A>C
  • NM_001406893.1:c.1602-2A>C
  • NM_001406894.1:c.1602-2A>C
  • NM_001406895.1:c.1602-2A>C
  • NM_001406896.1:c.1602-2A>C
  • NM_001406897.1:c.1602-2A>C
  • NM_001406898.1:c.1602-2A>C
  • NM_001406899.1:c.1602-2A>C
  • NM_001406900.1:c.1542-2A>C
  • NM_001406901.1:c.1533-2A>C
  • NM_001406902.1:c.1533-2A>C
  • NM_001406903.1:c.1688+3766A>C
  • NM_001406904.1:c.1494-2A>C
  • NM_001406905.1:c.1494-2A>C
  • NM_001406906.1:c.1446-2A>C
  • NM_001406907.1:c.1446-2A>C
  • NM_001406908.1:c.1601+3766A>C
  • NM_001406909.1:c.1434-2A>C
  • NM_001406910.1:c.1601+3766A>C
  • NM_001406911.1:c.1236-2A>C
  • NM_001406912.1:c.804-2A>C
  • LRG_161t1:c.2007-2A>C
  • LRG_161:g.31114A>C
  • NC_000007.13:g.6022624T>G
  • NM_000535.5:c.2007-2A>C
Links:
dbSNP: rs587782336
NCBI 1000 Genomes Browser:
rs587782336
Molecular consequence:
  • NM_001406872.1:c.2006+3766A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406903.1:c.1688+3766A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406908.1:c.1601+3766A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406910.1:c.1601+3766A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000535.7:c.2007-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322003.2:c.1602-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322004.2:c.1602-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322005.2:c.1602-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322006.2:c.1851-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322007.2:c.1689-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322008.2:c.1689-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322009.2:c.1602-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322010.2:c.1446-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322011.2:c.1074-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322012.2:c.1074-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322013.2:c.1434-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322014.2:c.2007-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322015.2:c.1698-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406866.1:c.2193-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406868.1:c.2031-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406869.1:c.1899-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406870.1:c.1851-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406871.1:c.2007-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406873.1:c.1809-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406874.1:c.1839-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406875.1:c.1698-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406876.1:c.1689-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406877.1:c.1698-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406878.1:c.1698-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406879.1:c.1698-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406880.1:c.1698-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406881.1:c.1698-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406882.1:c.1698-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406883.1:c.1689-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406884.1:c.1683-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406885.1:c.1671-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406886.1:c.1641-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406887.1:c.1602-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406888.1:c.1602-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406889.1:c.1602-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406890.1:c.1602-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406891.1:c.1602-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406892.1:c.1602-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406893.1:c.1602-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406894.1:c.1602-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406895.1:c.1602-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406896.1:c.1602-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406897.1:c.1602-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406898.1:c.1602-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406899.1:c.1602-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406900.1:c.1542-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406901.1:c.1533-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406902.1:c.1533-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406904.1:c.1494-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406905.1:c.1494-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406906.1:c.1446-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406907.1:c.1446-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406909.1:c.1434-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406911.1:c.1236-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001406912.1:c.804-2A>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
SCV000958901Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jul 26, 2023) 		germlineclinical testing

PubMed (3)
[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

Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients.

LaDuca H, Stuenkel AJ, Dolinsky JS, Keiles S, Tandy S, Pesaran T, Chen E, Gau CL, Palmaer E, Shoaepour K, Shah D, Speare V, Gandomi S, Chao E.

Genet Med. 2014 Nov;16(11):830-7. doi: 10.1038/gim.2014.40. Epub 2014 Apr 24.

PubMed [citation]
PMID:
24763289
PMCID:
PMC4225457

Constitutional mismatch repair deficiency syndrome: clinical description in a French cohort.

Lavoine N, Colas C, Muleris M, Bodo S, Duval A, Entz-Werle N, Coulet F, Cabaret O, Andreiuolo F, Charpy C, Sebille G, Wang Q, Lejeune S, Buisine MP, Leroux D, Couillault G, Leverger G, Fricker JP, Guimbaud R, Mathieu-Dramard M, Jedraszak G, Cohen-Hagenauer O, et al.

J Med Genet. 2015 Nov;52(11):770-8. doi: 10.1136/jmedgenet-2015-103299. Epub 2015 Aug 28. Review.

PubMed [citation]
PMID:
26318770
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000958901.6

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

Description

For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in activation of a cryptic splice site and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 142251). Disruption of this splice site has been observed in individuals with constitutional mismatch repair deficiency (CMMRD) syndrome or clinical features of PMS2-related conditions (PMID: 24763289, 26318770). The frequency data for this variant in the population databases (gnomAD) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This sequence change affects an acceptor splice site in intron 11 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.

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

Last Updated: Sep 29, 2024