NM_000535.7(PMS2):c.24-3T>C AND Hereditary nonpolyposis colorectal neoplasms

Clinical significance:Uncertain significance (Last evaluated: Aug 18, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000535.7(PMS2):c.24-3T>C]


PMS2:PMS1 homolog 2, mismatch repair system component [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
  • NC_000007.14:g.6006034A>G
  • NG_008466.1:g.8073T>C
  • NG_050738.1:g.1784A>G
  • NM_000535.7:c.24-3T>CMANE SELECT
  • NM_001322003.2:c.-377-8T>C
  • NM_001322004.2:c.-242-1976T>C
  • NM_001322005.2:c.-382-3T>C
  • NM_001322006.2:c.24-3T>C
  • NM_001322007.2:c.-192-3T>C
  • NM_001322008.2:c.-52-1976T>C
  • NM_001322009.2:c.-377-8T>C
  • NM_001322010.2:c.-242-1976T>C
  • NM_001322011.2:c.-861-3T>C
  • NM_001322012.2:c.-856-8T>C
  • NM_001322013.2:c.-377-8T>C
  • NM_001322014.2:c.24-3T>C
  • NM_001322015.2:c.-456-8T>C
  • LRG_161t1:c.24-3T>C
  • LRG_161:g.8073T>C
  • NC_000007.13:g.6045665A>G
  • NM_000535.5:c.24-3T>C
  • NM_000535.6:c.24-3T>C
dbSNP: rs749485884
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000535.7:c.24-3T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322003.2:c.-377-8T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322004.2:c.-242-1976T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322005.2:c.-382-3T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322006.2:c.24-3T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322007.2:c.-192-3T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322008.2:c.-52-1976T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322009.2:c.-377-8T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322010.2:c.-242-1976T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322011.2:c.-861-3T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322012.2:c.-856-8T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322013.2:c.-377-8T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322014.2:c.24-3T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322015.2:c.-456-8T>C - intron variant - [Sequence Ontology: SO:0001627]


Hereditary nonpolyposis colorectal neoplasms
MedGen: C0009405; Orphanet: 443090

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000285119Invitaecriteria provided, single submitter
Uncertain significance
(Aug 18, 2019)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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



Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

Details of each submission

From Invitae, SCV000285119.4

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


This sequence change falls in intron 1 of the PMS2 gene. It does not directly change the encoded amino acid sequence of the PMS2 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs749485884, ExAC 0.01%). This variant has not been reported in the literature in individuals with PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 237907). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Nov 27, 2021

Support Center