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NM_000535.7(PMS2):c.2007-2A>G AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 21, 2021
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:
RCV002423147.2

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

NM_000535.7(PMS2):c.2007-2A>G

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

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002719546Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Dec 21, 2021) 		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

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

No Overt Clinical Immunodeficiency Despite Immune Biological Abnormalities in Patients With Constitutional Mismatch Repair Deficiency.

Tesch VK, IJspeert H, Raicht A, Rueda D, Dominguez-Pinilla N, Allende LM, Colas C, Rosenbaum T, Ilencikova D, Baris HN, Nathrath MHM, Suerink M, Januszkiewicz-Lewandowska D, Ragab I, Azizi AA, Wenzel SS, Zschocke J, Schwinger W, Kloor M, Blattmann C, Brugieres L, van der Burg M, et al.

Front Immunol. 2018;9:1506. doi: 10.3389/fimmu.2018.01506.

PubMed [citation]
PMID:
30013564
PMCID:
PMC6036136
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002719546.2

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

Description

The c.2007-2A>G intronic pathogenic mutation results from an A to G substitution two nucleotides upstream from coding exon 12 in the PMS2 gene. Alterations that disrupt the canonical splice site are expected to result in aberrant splicing. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. The resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNAdecay; however, direct evidence is unavailable. The exact functional effect of the altered amino acid sequence is unknown; however, a significant portion of the protein is affected (Ambry internal data). This alteration has been identified homozygous in multiple individuals with CMMRD clinical diagnosis (Lavoine N et al. J Med Genet, 2015 Nov;52:770-8). This alteration has been reported in a patient with CRC at 45 years old and first degree relative(s) with CRC and endometrial cancer (Tesch VK et al. Front Immunol, 2018 Jul;9:1506). (Wang Q et al. J Med Genet, 2020 07;57:487-499). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Sep 29, 2024