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NM_000535.7(PMS2):c.2445+1G>C AND Hereditary nonpolyposis colon cancer

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Aug 29, 2022
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:
RCV001193217.3

Allele description [Variation Report for NM_000535.7(PMS2):c.2445+1G>C]

NM_000535.7(PMS2):c.2445+1G>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.2445+1G>C
HGVS:
  • NC_000007.14:g.5977587C>G
  • NG_008466.1:g.36520G>C
  • NM_000535.7:c.2445+1G>CMANE SELECT
  • NM_001322003.2:c.2040+1G>C
  • NM_001322004.2:c.2040+1G>C
  • NM_001322005.2:c.2040+1G>C
  • NM_001322006.2:c.2289+1G>C
  • NM_001322007.2:c.2127+1G>C
  • NM_001322008.2:c.2127+1G>C
  • NM_001322009.2:c.2073+1G>C
  • NM_001322010.2:c.1884+1G>C
  • NM_001322011.2:c.1512+1G>C
  • NM_001322012.2:c.1512+1G>C
  • NM_001322013.2:c.1872+1G>C
  • NM_001322014.2:c.2478+1G>C
  • NM_001322015.2:c.2136+1G>C
  • NM_001406866.1:c.2631+1G>C
  • NM_001406868.1:c.2469+1G>C
  • NM_001406869.1:c.2337+1G>C
  • NM_001406870.1:c.2322+1G>C
  • NM_001406871.1:c.2301+1G>C
  • NM_001406872.1:c.2277+1G>C
  • NM_001406873.1:c.2247+1G>C
  • NM_001406874.1:c.2277+1G>C
  • NM_001406875.1:c.2169+1G>C
  • NM_001406876.1:c.2160+1G>C
  • NM_001406877.1:c.2136+1G>C
  • NM_001406878.1:c.2136+1G>C
  • NM_001406879.1:c.2136+1G>C
  • NM_001406880.1:c.2136+1G>C
  • NM_001406881.1:c.2136+1G>C
  • NM_001406882.1:c.2136+1G>C
  • NM_001406883.1:c.2127+1G>C
  • NM_001406884.1:c.2121+1G>C
  • NM_001406885.1:c.2109+1G>C
  • NM_001406886.1:c.2079+1G>C
  • NM_001406887.1:c.2073+1G>C
  • NM_001406888.1:c.2073+1G>C
  • NM_001406889.1:c.2040+1G>C
  • NM_001406890.1:c.2040+1G>C
  • NM_001406891.1:c.2040+1G>C
  • NM_001406892.1:c.2040+1G>C
  • NM_001406893.1:c.2040+1G>C
  • NM_001406894.1:c.2040+1G>C
  • NM_001406895.1:c.2040+1G>C
  • NM_001406896.1:c.2040+1G>C
  • NM_001406897.1:c.2040+1G>C
  • NM_001406898.1:c.2040+1G>C
  • NM_001406899.1:c.2040+1G>C
  • NM_001406900.1:c.1980+1G>C
  • NM_001406901.1:c.1971+1G>C
  • NM_001406902.1:c.1971+1G>C
  • NM_001406903.1:c.1959+1G>C
  • NM_001406904.1:c.1932+1G>C
  • NM_001406905.1:c.1932+1G>C
  • NM_001406906.1:c.1884+1G>C
  • NM_001406907.1:c.1884+1G>C
  • NM_001406908.1:c.1872+1G>C
  • NM_001406909.1:c.1872+1G>C
  • NM_001406910.1:c.1728+1G>C
  • NM_001406911.1:c.1674+1G>C
  • NM_001406912.1:c.1242+1G>C
  • LRG_161t1:c.2445+1G>C
  • LRG_161:g.36520G>C
  • NC_000007.13:g.6017218C>G
  • NM_000535.5:c.2445+1G>C
  • NM_000535.6:c.2445+1G>C
Links:
dbSNP: rs876661113
NCBI 1000 Genomes Browser:
rs876661113
Molecular consequence:
  • NM_000535.7:c.2445+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322003.2:c.2040+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322004.2:c.2040+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322005.2:c.2040+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322006.2:c.2289+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322007.2:c.2127+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322008.2:c.2127+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322009.2:c.2073+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322010.2:c.1884+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322011.2:c.1512+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322012.2:c.1512+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322013.2:c.1872+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322014.2:c.2478+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322015.2:c.2136+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406866.1:c.2631+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406868.1:c.2469+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406869.1:c.2337+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406870.1:c.2322+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406871.1:c.2301+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406872.1:c.2277+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406873.1:c.2247+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406874.1:c.2277+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406875.1:c.2169+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406876.1:c.2160+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406877.1:c.2136+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406878.1:c.2136+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406879.1:c.2136+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406880.1:c.2136+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406881.1:c.2136+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406882.1:c.2136+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406883.1:c.2127+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406884.1:c.2121+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406885.1:c.2109+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406886.1:c.2079+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406887.1:c.2073+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406888.1:c.2073+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406889.1:c.2040+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406890.1:c.2040+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406891.1:c.2040+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406892.1:c.2040+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406893.1:c.2040+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406894.1:c.2040+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406895.1:c.2040+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406896.1:c.2040+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406897.1:c.2040+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406898.1:c.2040+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406899.1:c.2040+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406900.1:c.1980+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406901.1:c.1971+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406902.1:c.1971+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406903.1:c.1959+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406904.1:c.1932+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406905.1:c.1932+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406906.1:c.1884+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406907.1:c.1884+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406908.1:c.1872+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406909.1:c.1872+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406910.1:c.1728+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406911.1:c.1674+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406912.1:c.1242+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Hereditary nonpolyposis colon cancer (HNPCC)
Synonyms:
Hereditary nonpolyposis colorectal cancer; Familial nonpolyposis colon cancer; Hereditary Nonpolyposis Colorectal Cancer Syndrome
Identifiers:
MONDO: MONDO:0018630; MedGen: C1333990; OMIM: PS120435

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001361926Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely pathogenic
(Aug 29, 2022) 		germlineclinical testing

Citation Link

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Summary from all submissions

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001361926.2

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

Description

Variant summary: PMS2 c.2445+1G>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 194842 control chromosomes. To our knowledge, no occurrence of c.2445+1G>C in individuals affected with Hereditary Nonpolyposis Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

Last Updated: Sep 29, 2024