NM_000535.7(PMS2):c.2445+1G>T AND Hereditary nonpolyposis colorectal neoplasms
- Germline classification:
- Pathogenic (1 submission)
- Last evaluated:
- Jan 25, 2024
- Review status:
- 1 star out of maximum of 4 starscriteria provided, single submitter
- Somatic classification
of clinical impact: - None
- Review status:
- (0/4) 0 stars out of maximum of 4 starsno assertion criteria provided
- Somatic classification
of oncogenicity: - None
- Review status:
- (0/4) 0 stars out of maximum of 4 starsno assertion criteria provided
- Record status:
- current
- Accession:
- RCV000228982.13
Allele description [Variation Report for NM_000535.7(PMS2):c.2445+1G>T]
NM_000535.7(PMS2):c.2445+1G>T
- 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>T
- HGVS:
- NC_000007.14:g.5977587C>A
- NG_008466.1:g.36520G>T
- NM_000535.7:c.2445+1G>TMANE SELECT
- NM_001322003.2:c.2040+1G>T
- NM_001322004.2:c.2040+1G>T
- NM_001322005.2:c.2040+1G>T
- NM_001322006.2:c.2289+1G>T
- NM_001322007.2:c.2127+1G>T
- NM_001322008.2:c.2127+1G>T
- NM_001322009.2:c.2073+1G>T
- NM_001322010.2:c.1884+1G>T
- NM_001322011.2:c.1512+1G>T
- NM_001322012.2:c.1512+1G>T
- NM_001322013.2:c.1872+1G>T
- NM_001322014.2:c.2478+1G>T
- NM_001322015.2:c.2136+1G>T
- NM_001406866.1:c.2631+1G>T
- NM_001406868.1:c.2469+1G>T
- NM_001406869.1:c.2337+1G>T
- NM_001406870.1:c.2322+1G>T
- NM_001406871.1:c.2301+1G>T
- NM_001406872.1:c.2277+1G>T
- NM_001406873.1:c.2247+1G>T
- NM_001406874.1:c.2277+1G>T
- NM_001406875.1:c.2169+1G>T
- NM_001406876.1:c.2160+1G>T
- NM_001406877.1:c.2136+1G>T
- NM_001406878.1:c.2136+1G>T
- NM_001406879.1:c.2136+1G>T
- NM_001406880.1:c.2136+1G>T
- NM_001406881.1:c.2136+1G>T
- NM_001406882.1:c.2136+1G>T
- NM_001406883.1:c.2127+1G>T
- NM_001406884.1:c.2121+1G>T
- NM_001406885.1:c.2109+1G>T
- NM_001406886.1:c.2079+1G>T
- NM_001406887.1:c.2073+1G>T
- NM_001406888.1:c.2073+1G>T
- NM_001406889.1:c.2040+1G>T
- NM_001406890.1:c.2040+1G>T
- NM_001406891.1:c.2040+1G>T
- NM_001406892.1:c.2040+1G>T
- NM_001406893.1:c.2040+1G>T
- NM_001406894.1:c.2040+1G>T
- NM_001406895.1:c.2040+1G>T
- NM_001406896.1:c.2040+1G>T
- NM_001406897.1:c.2040+1G>T
- NM_001406898.1:c.2040+1G>T
- NM_001406899.1:c.2040+1G>T
- NM_001406900.1:c.1980+1G>T
- NM_001406901.1:c.1971+1G>T
- NM_001406902.1:c.1971+1G>T
- NM_001406903.1:c.1959+1G>T
- NM_001406904.1:c.1932+1G>T
- NM_001406905.1:c.1932+1G>T
- NM_001406906.1:c.1884+1G>T
- NM_001406907.1:c.1884+1G>T
- NM_001406908.1:c.1872+1G>T
- NM_001406909.1:c.1872+1G>T
- NM_001406910.1:c.1728+1G>T
- NM_001406911.1:c.1674+1G>T
- NM_001406912.1:c.1242+1G>T
- LRG_161t1:c.2445+1G>T
- LRG_161:g.36520G>T
- NC_000007.13:g.6017218C>A
- NM_000535.5:c.2445+1G>T
- NM_000535.6:c.2445+1G>T
This HGVS expression did not pass validation- Links:
- dbSNP: rs876661113
- NCBI 1000 Genomes Browser:
- rs876661113
- Molecular consequence:
- NM_000535.7:c.2445+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322003.2:c.2040+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322004.2:c.2040+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322005.2:c.2040+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322006.2:c.2289+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322007.2:c.2127+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322008.2:c.2127+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322009.2:c.2073+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322010.2:c.1884+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322011.2:c.1512+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322012.2:c.1512+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322013.2:c.1872+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322014.2:c.2478+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322015.2:c.2136+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406866.1:c.2631+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406868.1:c.2469+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406869.1:c.2337+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406870.1:c.2322+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406871.1:c.2301+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406872.1:c.2277+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406873.1:c.2247+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406874.1:c.2277+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406875.1:c.2169+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406876.1:c.2160+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406877.1:c.2136+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406878.1:c.2136+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406879.1:c.2136+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406880.1:c.2136+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406881.1:c.2136+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406882.1:c.2136+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406883.1:c.2127+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406884.1:c.2121+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406885.1:c.2109+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406886.1:c.2079+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406887.1:c.2073+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406888.1:c.2073+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406889.1:c.2040+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406890.1:c.2040+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406891.1:c.2040+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406892.1:c.2040+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406893.1:c.2040+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406894.1:c.2040+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406895.1:c.2040+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406896.1:c.2040+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406897.1:c.2040+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406898.1:c.2040+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406899.1:c.2040+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406900.1:c.1980+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406901.1:c.1971+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406902.1:c.1971+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406903.1:c.1959+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406904.1:c.1932+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406905.1:c.1932+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406906.1:c.1884+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406907.1:c.1884+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406908.1:c.1872+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406909.1:c.1872+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406910.1:c.1728+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406911.1:c.1674+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406912.1:c.1242+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
Condition(s)
- Name:
- Hereditary nonpolyposis colorectal neoplasms
- Identifiers:
- MeSH: D003123; MedGen: C0009405
-
ABRACL ABRA C-terminal like [Bos taurus]
ABRACL ABRA C-terminal like [Bos taurus]Gene ID:505914Gene
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See more...Assertion and evidence details
| Submission Accession | Submitter | Review Status (Assertion method) | Clinical Significance (Last evaluated) | Origin | Method | Citations |
|---|---|---|---|---|---|---|
| SCV000285122 | Invitae | criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) | Pathogenic (Jan 25, 2024) | germline | clinical testing |
Summary from all submissions
| Ethnicity | Origin | Affected | Individuals | Families | Chromosomes tested | Number Tested | Family history | Method |
|---|---|---|---|---|---|---|---|---|
| not provided | germline | unknown | not provided | not provided | not provided | not provided | not provided | clinical testing |
Citations
PubMed
PMS2 involvement in patients suspected of Lynch syndrome.
Niessen RC, Kleibeuker JH, Westers H, Jager PO, Rozeveld D, Bos KK, Boersma-van Ek W, Hollema H, Sijmons RH, Hofstra RM.
Genes Chromosomes Cancer. 2009 Apr;48(4):322-9. doi: 10.1002/gcc.20642.
PubMed [citation]
- PMID:
- 19132747
Clinical analysis of PMS2: mutation detection and avoidance of pseudogenes.
Vaughn CP, Robles J, Swensen JJ, Miller CE, Lyon E, Mao R, Bayrak-Toydemir P, Samowitz WS.
Hum Mutat. 2010 May;31(5):588-93. doi: 10.1002/humu.21230.
PubMed [citation]
- PMID:
- 20205264
Details of each submission
From Invitae, SCV000285122.11
| # | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
|---|---|---|---|---|---|---|
| 1 | not provided | not provided | not provided | not provided | clinical testing | PubMed (14) |
Description
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. 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. Disruption of this splice site has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 19132747, 20205264, 23012243, 25512458, 26110232). ClinVar contains an entry for this variant (Variation ID: 234604). 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 activation of a cryptic splice site and introduces a new termination codon (PMID: 26247049; Invitae). However the mRNA is not expected to undergo nonsense-mediated decay. 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. For these reasons, this variant has been classified as Pathogenic.
| # | Sample | Method | Observation | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
| 1 | germline | unknown | not provided | not provided | not provided | not provided | not provided | not provided | not provided | |
Last Updated: Sep 16, 2024