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NM_000535.7(PMS2):c.2007-4_2007-1delinsACAC AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jul 24, 2018
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:
RCV000707117.7

Allele description [Variation Report for NM_000535.7(PMS2):c.2007-4_2007-1delinsACAC]

NM_000535.7(PMS2):c.2007-4_2007-1delinsACAC

Gene:
PMS2:PMS1 homolog 2, mismatch repair system component [Gene - OMIM - HGNC]
Variant type:
Indel
Cytogenetic location:
7p22.1
Genomic location:
Preferred name:
NM_000535.7(PMS2):c.2007-4_2007-1delinsACAC
HGVS:
  • NC_000007.14:g.5982992_5982995delinsGTGT
  • NG_008466.1:g.31112_31115delinsACAC
  • NM_000535.7:c.2007-4_2007-1delinsACACMANE SELECT
  • NM_001322003.2:c.1602-4_1602-1delinsACAC
  • NM_001322004.2:c.1602-4_1602-1delinsACAC
  • NM_001322005.2:c.1602-4_1602-1delinsACAC
  • NM_001322006.2:c.1851-4_1851-1delinsACAC
  • NM_001322007.2:c.1689-4_1689-1delinsACAC
  • NM_001322008.2:c.1689-4_1689-1delinsACAC
  • NM_001322009.2:c.1602-4_1602-1delinsACAC
  • NM_001322010.2:c.1446-4_1446-1delinsACAC
  • NM_001322011.2:c.1074-4_1074-1delinsACAC
  • NM_001322012.2:c.1074-4_1074-1delinsACAC
  • NM_001322013.2:c.1434-4_1434-1delinsACAC
  • NM_001322014.2:c.2007-4_2007-1delinsACAC
  • NM_001322015.2:c.1698-4_1698-1delinsACAC
  • LRG_161t1:c.2007-4_2007-1delinsACAC
  • LRG_161:g.31112_31115delinsACAC
  • NC_000007.13:g.6022623_6022626delCTGCinsGTGT
  • NC_000007.13:g.6022623_6022626delinsGTGT
  • NM_000535.5:c.2007-4_2007-1delinsACAC
Links:
dbSNP: rs1562616355
NCBI 1000 Genomes Browser:
rs1562616355
Molecular consequence:
  • NM_000535.7:c.2007-4_2007-1delinsACAC - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322003.2:c.1602-4_1602-1delinsACAC - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322004.2:c.1602-4_1602-1delinsACAC - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322005.2:c.1602-4_1602-1delinsACAC - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322006.2:c.1851-4_1851-1delinsACAC - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322007.2:c.1689-4_1689-1delinsACAC - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322008.2:c.1689-4_1689-1delinsACAC - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322009.2:c.1602-4_1602-1delinsACAC - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322010.2:c.1446-4_1446-1delinsACAC - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322011.2:c.1074-4_1074-1delinsACAC - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322012.2:c.1074-4_1074-1delinsACAC - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322013.2:c.1434-4_1434-1delinsACAC - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322014.2:c.2007-4_2007-1delinsACAC - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001322015.2:c.1698-4_1698-1delinsACAC - 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
SCV000836200Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Jul 24, 2018) 		germlineclinical testing

PubMed (4)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Paediatric intestinal cancer and polyposis due to bi-allelic PMS2 mutations: case series, review and follow-up guidelines.

Herkert JC, Niessen RC, Olderode-Berends MJ, Veenstra-Knol HE, Vos YJ, van der Klift HM, Scheenstra R, Tops CM, Karrenbeld A, Peters FT, Hofstra RM, Kleibeuker JH, Sijmons RH.

Eur J Cancer. 2011 May;47(7):965-82. doi: 10.1016/j.ejca.2011.01.013. Epub 2011 Mar 4. Review.

PubMed [citation]
PMID:
21376568
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000836200.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This variant has not been reported in the literature in individuals with PMS2-related disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). This variant is not present in population databases (ExAC no frequency). However, the frequency data 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. It is expected to disrupt RNA splicing and likely results 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