NM_000535.7(PMS2):c.2006+1G>C AND Hereditary nonpolyposis colorectal neoplasms
- Germline classification:
- Likely pathogenic (1 submission)
- Last evaluated:
- Jul 30, 2020
- 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:
- RCV000533158.7
Allele description [Variation Report for NM_000535.7(PMS2):c.2006+1G>C]
NM_000535.7(PMS2):c.2006+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.2006+1G>C
- HGVS:
- NC_000007.14:g.5986758C>G
- NG_008466.1:g.27349G>C
- NM_000535.7:c.2006+1G>CMANE SELECT
- NM_001322003.2:c.1601+1G>C
- NM_001322004.2:c.1601+1G>C
- NM_001322005.2:c.1601+1G>C
- NM_001322006.2:c.1850+1G>C
- NM_001322007.2:c.1688+1G>C
- NM_001322008.2:c.1688+1G>C
- NM_001322009.2:c.1601+1G>C
- NM_001322010.2:c.1445+1G>C
- NM_001322011.2:c.1073+1G>C
- NM_001322012.2:c.1073+1G>C
- NM_001322013.2:c.1433+1G>C
- NM_001322014.2:c.2006+1G>C
- NM_001322015.2:c.1697+1G>C
- NM_001406866.1:c.2192+1G>C
- NM_001406868.1:c.2030+1G>C
- NM_001406869.1:c.1898+1G>C
- NM_001406870.1:c.1850+1G>C
- NM_001406871.1:c.2006+1G>C
- NM_001406872.1:c.2006+1G>C
- NM_001406873.1:c.1808+1G>C
- NM_001406874.1:c.1838+1G>C
- NM_001406875.1:c.1697+1G>C
- NM_001406876.1:c.1688+1G>C
- NM_001406877.1:c.1697+1G>C
- NM_001406878.1:c.1697+1G>C
- NM_001406879.1:c.1697+1G>C
- NM_001406880.1:c.1697+1G>C
- NM_001406881.1:c.1697+1G>C
- NM_001406882.1:c.1697+1G>C
- NM_001406883.1:c.1688+1G>C
- NM_001406884.1:c.1682+1G>C
- NM_001406885.1:c.1670+1G>C
- NM_001406886.1:c.1640+1G>C
- NM_001406887.1:c.1601+1G>C
- NM_001406888.1:c.1601+1G>C
- NM_001406889.1:c.1601+1G>C
- NM_001406890.1:c.1601+1G>C
- NM_001406891.1:c.1601+1G>C
- NM_001406892.1:c.1601+1G>C
- NM_001406893.1:c.1601+1G>C
- NM_001406894.1:c.1601+1G>C
- NM_001406895.1:c.1601+1G>C
- NM_001406896.1:c.1601+1G>C
- NM_001406897.1:c.1601+1G>C
- NM_001406898.1:c.1601+1G>C
- NM_001406899.1:c.1601+1G>C
- NM_001406900.1:c.1541+1G>C
- NM_001406901.1:c.1532+1G>C
- NM_001406902.1:c.1532+1G>C
- NM_001406903.1:c.1688+1G>C
- NM_001406904.1:c.1493+1G>C
- NM_001406905.1:c.1493+1G>C
- NM_001406906.1:c.1445+1G>C
- NM_001406907.1:c.1445+1G>C
- NM_001406908.1:c.1601+1G>C
- NM_001406909.1:c.1433+1G>C
- NM_001406910.1:c.1601+1G>C
- NM_001406911.1:c.1235+1G>C
- NM_001406912.1:c.804-3767G>C
- LRG_161t1:c.2006+1G>C
- LRG_161:g.27349G>C
- NC_000007.13:g.6026389C>G
- NM_000535.5:c.2006+1G>C
This HGVS expression did not pass validation- Links:
- dbSNP: rs1554297040
- NCBI 1000 Genomes Browser:
- rs1554297040
- Molecular consequence:
- NM_001406912.1:c.804-3767G>C - intron variant - [Sequence Ontology: SO:0001627]
- NM_000535.7:c.2006+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322003.2:c.1601+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322004.2:c.1601+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322005.2:c.1601+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322006.2:c.1850+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322007.2:c.1688+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322008.2:c.1688+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322009.2:c.1601+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322010.2:c.1445+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322011.2:c.1073+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322012.2:c.1073+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322013.2:c.1433+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322014.2:c.2006+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001322015.2:c.1697+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406866.1:c.2192+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406868.1:c.2030+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406869.1:c.1898+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406870.1:c.1850+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406871.1:c.2006+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406872.1:c.2006+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406873.1:c.1808+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406874.1:c.1838+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406875.1:c.1697+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406876.1:c.1688+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406877.1:c.1697+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406878.1:c.1697+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406879.1:c.1697+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406880.1:c.1697+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406881.1:c.1697+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406882.1:c.1697+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406883.1:c.1688+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406884.1:c.1682+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406885.1:c.1670+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406886.1:c.1640+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406887.1:c.1601+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406888.1:c.1601+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406889.1:c.1601+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406890.1:c.1601+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406891.1:c.1601+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406892.1:c.1601+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406893.1:c.1601+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406894.1:c.1601+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406895.1:c.1601+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406896.1:c.1601+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406897.1:c.1601+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406898.1:c.1601+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406899.1:c.1601+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406900.1:c.1541+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406901.1:c.1532+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406902.1:c.1532+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406903.1:c.1688+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406904.1:c.1493+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406905.1:c.1493+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406906.1:c.1445+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406907.1:c.1445+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406908.1:c.1601+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406909.1:c.1433+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406910.1:c.1601+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
- NM_001406911.1:c.1235+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
Condition(s)
- Name:
- Hereditary nonpolyposis colorectal neoplasms
- Identifiers:
- MeSH: D003123; MedGen: C0009405
Assertion and evidence details
Submission Accession | Submitter | Review Status (Assertion method) | Clinical Significance (Last evaluated) | Origin | Method | Citations |
---|---|---|---|---|---|---|
SCV000625576 | Invitae | criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) | Likely pathogenic (Jul 30, 2020) | 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
Splicing in action: assessing disease causing sequence changes.
Baralle D, Baralle M.
J Med Genet. 2005 Oct;42(10):737-48. Review.
- PMID:
- 16199547
- PMCID:
- PMC1735933
Herkert JC, Niessen RC, Olderode-Berends MJ, Veenstra-Knol HE, Vos YJ, van der Klift HM, Scheenstra R, Tops CM, Karrenbeld A, Peters FT, Hofstra RM, Kleibeuker JH, Sijmons RH.
Eur J Cancer. 2011 May;47(7):965-82. doi: 10.1016/j.ejca.2011.01.013. Epub 2011 Mar 4. Review.
- PMID:
- 21376568
Details of each submission
From Invitae, SCV000625576.7
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | PubMed (4) |
Description
In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 455680). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 11 of the PMS2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.
# | 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: Feb 20, 2024