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NM_000535.7(PMS2):c.2445+1G>A AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 18, 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:
RCV001386315.7

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

NM_000535.7(PMS2):c.2445+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_000535.7(PMS2):c.2445+1G>A
HGVS:
  • NC_000007.14:g.5977587C>T
  • NG_008466.1:g.36520G>A
  • NM_000535.7:c.2445+1G>AMANE SELECT
  • NM_001322003.2:c.2040+1G>A
  • NM_001322004.2:c.2040+1G>A
  • NM_001322005.2:c.2040+1G>A
  • NM_001322006.2:c.2289+1G>A
  • NM_001322007.2:c.2127+1G>A
  • NM_001322008.2:c.2127+1G>A
  • NM_001322009.2:c.2073+1G>A
  • NM_001322010.2:c.1884+1G>A
  • NM_001322011.2:c.1512+1G>A
  • NM_001322012.2:c.1512+1G>A
  • NM_001322013.2:c.1872+1G>A
  • NM_001322014.2:c.2478+1G>A
  • NM_001322015.2:c.2136+1G>A
  • NM_001406866.1:c.2631+1G>A
  • NM_001406868.1:c.2469+1G>A
  • NM_001406869.1:c.2337+1G>A
  • NM_001406870.1:c.2322+1G>A
  • NM_001406871.1:c.2301+1G>A
  • NM_001406872.1:c.2277+1G>A
  • NM_001406873.1:c.2247+1G>A
  • NM_001406874.1:c.2277+1G>A
  • NM_001406875.1:c.2169+1G>A
  • NM_001406876.1:c.2160+1G>A
  • NM_001406877.1:c.2136+1G>A
  • NM_001406878.1:c.2136+1G>A
  • NM_001406879.1:c.2136+1G>A
  • NM_001406880.1:c.2136+1G>A
  • NM_001406881.1:c.2136+1G>A
  • NM_001406882.1:c.2136+1G>A
  • NM_001406883.1:c.2127+1G>A
  • NM_001406884.1:c.2121+1G>A
  • NM_001406885.1:c.2109+1G>A
  • NM_001406886.1:c.2079+1G>A
  • NM_001406887.1:c.2073+1G>A
  • NM_001406888.1:c.2073+1G>A
  • NM_001406889.1:c.2040+1G>A
  • NM_001406890.1:c.2040+1G>A
  • NM_001406891.1:c.2040+1G>A
  • NM_001406892.1:c.2040+1G>A
  • NM_001406893.1:c.2040+1G>A
  • NM_001406894.1:c.2040+1G>A
  • NM_001406895.1:c.2040+1G>A
  • NM_001406896.1:c.2040+1G>A
  • NM_001406897.1:c.2040+1G>A
  • NM_001406898.1:c.2040+1G>A
  • NM_001406899.1:c.2040+1G>A
  • NM_001406900.1:c.1980+1G>A
  • NM_001406901.1:c.1971+1G>A
  • NM_001406902.1:c.1971+1G>A
  • NM_001406903.1:c.1959+1G>A
  • NM_001406904.1:c.1932+1G>A
  • NM_001406905.1:c.1932+1G>A
  • NM_001406906.1:c.1884+1G>A
  • NM_001406907.1:c.1884+1G>A
  • NM_001406908.1:c.1872+1G>A
  • NM_001406909.1:c.1872+1G>A
  • NM_001406910.1:c.1728+1G>A
  • NM_001406911.1:c.1674+1G>A
  • NM_001406912.1:c.1242+1G>A
  • LRG_161t1:c.2445+1G>A
  • LRG_161:g.36520G>A
  • NC_000007.13:g.6017218C>T
  • NM_000535.5:c.2445+1G>A
Links:
dbSNP: rs876661113
NCBI 1000 Genomes Browser:
rs876661113
Molecular consequence:
  • NM_000535.7:c.2445+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322003.2:c.2040+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322004.2:c.2040+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322005.2:c.2040+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322006.2:c.2289+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322007.2:c.2127+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322008.2:c.2127+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322009.2:c.2073+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322010.2:c.1884+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322011.2:c.1512+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322012.2:c.1512+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322013.2:c.1872+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322014.2:c.2478+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001322015.2:c.2136+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406866.1:c.2631+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406868.1:c.2469+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406869.1:c.2337+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406870.1:c.2322+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406871.1:c.2301+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406872.1:c.2277+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406873.1:c.2247+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406874.1:c.2277+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406875.1:c.2169+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406876.1:c.2160+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406877.1:c.2136+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406878.1:c.2136+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406879.1:c.2136+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406880.1:c.2136+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406881.1:c.2136+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406882.1:c.2136+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406883.1:c.2127+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406884.1:c.2121+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406885.1:c.2109+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406886.1:c.2079+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406887.1:c.2073+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406888.1:c.2073+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406889.1:c.2040+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406890.1:c.2040+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406891.1:c.2040+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406892.1:c.2040+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406893.1:c.2040+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406894.1:c.2040+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406895.1:c.2040+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406896.1:c.2040+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406897.1:c.2040+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406898.1:c.2040+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406899.1:c.2040+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406900.1:c.1980+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406901.1:c.1971+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406902.1:c.1971+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406903.1:c.1959+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406904.1:c.1932+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406905.1:c.1932+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406906.1:c.1884+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406907.1:c.1884+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406908.1:c.1872+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406909.1:c.1872+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406910.1:c.1728+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406911.1:c.1674+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406912.1:c.1242+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV001586503Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Feb 18, 2022) 		germlineclinical testing

PubMed (9)
[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

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]
PMID:
9536098
See all PubMed Citations (9)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001586503.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that disruption of this splice site results in the retention of 85 base pairs and the production of aberrant transcripts and introduces a new termination codon (PMID: 26247049). However the mRNA is not expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 484307). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. The frequency data for this variant in the population databases (gnomAD) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This sequence change affects a donor splice site in intron 14 of the PMS2 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely disrupts the C-terminus of the protein. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PMS2 protein in which other variant(s) (p.Trp841Glyfs*10) have been determined to be pathogenic (PMID: 10037723, 16338176, 20533529, 26116798, 28218421). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing.

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

Last Updated: Sep 29, 2024