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NM_000535.5(PMS2):c.2174+1G>A AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 8, 2017
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:
RCV000115677.2

Allele description

NM_000535.5(PMS2):c.2174+1G>A

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_000535.5(PMS2):c.2174+1G>A
Other names:
IVS12+1G>A
HGVS:
  • NC_000007.14:g.5982823C>T
  • NG_008466.1:g.31284G>A
  • NM_000535.6:c.2174+1G>A
  • LRG_161t1:c.2174+1G>A
  • LRG_161:g.31284G>A
  • NC_000007.13:g.6022454C>T
  • NM_000535.5:c.2174+1G>A
Links:
dbSNP: rs267608172
NCBI 1000 Genomes Browser:
rs267608172
Molecular consequence:
  • NM_000535.5:c.2174+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000149586GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Pathogenic
(May 8, 2017) 		germlineclinical testing

Citation Link

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Summary from all submissions

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

Details of each submission

From GeneDx, SCV000149586.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is denoted PMS2 c.2174+1G>A or IVS12+1G>A and consists of a G>A nucleotide substitution at the +1 position of intron 12 of the PMS2 gene. This variant destroys a canonical splice donor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. Functional studies, including a splicing analysis using patient RNA and an in vitro minigene assay, have demonstrated aberrant splicing (van der Klift 2015). The International Society for Gastrointestinal Hereditary Tumours Incorporated (InSiGHT) classifies this variant as pathogenic (Thompson 2014). In the heterozygous state, PMS2 c.2174+1G>A has been reported in association with Lynch syndrome, and, in both the compound heterozygous and homozygous states, it has been observed in individuals with constitutional mismatch repair deficiency (CMMR-D) syndrome (Senter 2008, Vaughn 2010, Herkert 2011). Based on the current evidence, we consider this variant to be pathogenic.

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

Last Updated: Mar 31, 2019