NM_000535.7(PMS2):c.66_69del (p.Val23fs) AND Hereditary nonpolyposis colorectal neoplasms
- Germline classification:
- Pathogenic (1 submission)
- Last evaluated:
- Oct 26, 2023
- 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:
- RCV003594463.2
Allele description [Variation Report for NM_000535.7(PMS2):c.66_69del (p.Val23fs)]
NM_000535.7(PMS2):c.66_69del (p.Val23fs)
- Gene:
- PMS2:PMS1 homolog 2, mismatch repair system component [Gene - OMIM - HGNC]
- Variant type:
- Microsatellite
- Cytogenetic location:
- 7p22.1
- Genomic location:
- Preferred name:
- NM_000535.7(PMS2):c.66_69del (p.Val23fs)
- HGVS:
- NC_000007.14:g.6005986GACT[1]
- NG_008466.1:g.8114AGTC[1]
- NG_050738.1:g.1736GACT[1]
- NM_000535.7:c.66_69delMANE SELECT
- NM_001018040.1:c.-344_-341AGTC[1]
- NM_001322003.2:c.-344AGTC[1]
- NM_001322004.2:c.-242-1931_-242-1928del
- NM_001322005.2:c.-344AGTC[1]
- NM_001322006.2:c.66_69del
- NM_001322007.2:c.-154AGTC[1]
- NM_001322008.2:c.-52-1931_-52-1928del
- NM_001322009.2:c.-344AGTC[1]
- NM_001322010.2:c.-242-1931_-242-1928del
- NM_001322011.2:c.-823AGTC[1]
- NM_001322012.2:c.-823AGTC[1]
- NM_001322013.2:c.-344AGTC[1]
- NM_001322014.2:c.66_69del
- NM_001322015.2:c.-423AGTC[1]
- NM_001406866.1:c.252_255del
- NM_001406868.1:c.66_69del
- NM_001406869.1:c.66_69del
- NM_001406870.1:c.66_69del
- NM_001406871.1:c.66_69del
- NM_001406872.1:c.66_69del
- NM_001406873.1:c.66_69del
- NM_001406874.1:c.66_69del
- NM_001406875.1:c.-423AGTC[1]
- NM_001406876.1:c.-154AGTC[1]
- NM_001406877.1:c.-423AGTC[1]
- NM_001406878.1:c.-423AGTC[1]
- NM_001406879.1:c.-321-1931_-321-1928del
- NM_001406880.1:c.-370AGTC[1]
- NM_001406881.1:c.-218-1931_-218-1928del
- NM_001406882.1:c.-423AGTC[1]
- NM_001406883.1:c.-154AGTC[1]
- NM_001406884.1:c.66_69del
- NM_001406885.1:c.66_69del
- NM_001406886.1:c.66_69del
- NM_001406887.1:c.-344AGTC[1]
- NM_001406888.1:c.-291AGTC[1]
- NM_001406889.1:c.-291AGTC[1]
- NM_001406890.1:c.-334AGTC[1]
- NM_001406891.1:c.-344AGTC[1]
- NM_001406892.1:c.-291AGTC[1]
- NM_001406893.1:c.-344AGTC[1]
- NM_001406894.1:c.-291AGTC[1]
- NM_001406895.1:c.-189-1931_-189-1928del
- NM_001406896.1:c.-154AGTC[1]
- NM_001406897.1:c.-344AGTC[1]
- NM_001406898.1:c.-344AGTC[1]
- NM_001406899.1:c.-291AGTC[1]
- NM_001406900.1:c.-320AGTC[1]
- NM_001406901.1:c.-154AGTC[1]
- NM_001406902.1:c.-154AGTC[1]
- NM_001406903.1:c.-154AGTC[1]
- NM_001406904.1:c.-291AGTC[1]
- NM_001406905.1:c.-344AGTC[1]
- NM_001406906.1:c.-344AGTC[1]
- NM_001406907.1:c.-291AGTC[1]
- NM_001406908.1:c.-344AGTC[1]
- NM_001406909.1:c.-291AGTC[1]
- NM_001406910.1:c.-344AGTC[1]
- NM_001406911.1:c.-242-1931_-242-1928del
- NM_001406912.1:c.66_69del
- NP_000526.1:p.Val23Ilefs
- NP_000526.2:p.Val23fs
- NP_001308935.1:p.Val23fs
- NP_001308943.1:p.Val23fs
- NP_001393795.1:p.Val85fs
- NP_001393797.1:p.Val23fs
- NP_001393798.1:p.Val23fs
- NP_001393799.1:p.Val23fs
- NP_001393800.1:p.Val23fs
- NP_001393801.1:p.Val23fs
- NP_001393802.1:p.Val23fs
- NP_001393803.1:p.Val23fs
- NP_001393813.1:p.Val23fs
- NP_001393814.1:p.Val23fs
- NP_001393815.1:p.Val23fs
- NP_001393841.1:p.Val23fs
- LRG_161t1:c.62_65AGTC[1]
- LRG_161:g.8114AGTC[1]
- LRG_161p1:p.Val23Ilefs
- NC_000007.13:g.6045617GACT[1]
- NC_000007.13:g.6045617_6045620del
- NM_000535.5:c.62_65AGTC[1]
- NR_003085.2:n.144_147AGTC[1]
- NR_136154.1:n.149AGTC[1]
This HGVS expression did not pass validation- Protein change:
- V23fs
- Molecular consequence:
- NM_001322003.2:c.-344AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001322005.2:c.-344AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001322007.2:c.-154AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001322009.2:c.-344AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001322011.2:c.-823AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001322012.2:c.-823AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001322013.2:c.-344AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001322015.2:c.-423AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406875.1:c.-423AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406876.1:c.-154AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406877.1:c.-423AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406878.1:c.-423AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406880.1:c.-370AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406882.1:c.-423AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406883.1:c.-154AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406887.1:c.-344AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406888.1:c.-291AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406889.1:c.-291AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406890.1:c.-334AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406891.1:c.-344AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406892.1:c.-291AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406893.1:c.-344AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406894.1:c.-291AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406896.1:c.-154AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406897.1:c.-344AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406898.1:c.-344AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406899.1:c.-291AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406900.1:c.-320AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406901.1:c.-154AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406902.1:c.-154AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406903.1:c.-154AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406904.1:c.-291AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406905.1:c.-344AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406906.1:c.-344AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406907.1:c.-291AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406908.1:c.-344AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406909.1:c.-291AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_001406910.1:c.-344AGTC[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
- NM_000535.7:c.66_69del - frameshift variant - [Sequence Ontology: SO:0001589]
- NM_001322006.2:c.66_69del - frameshift variant - [Sequence Ontology: SO:0001589]
- NM_001322014.2:c.66_69del - frameshift variant - [Sequence Ontology: SO:0001589]
- NM_001406866.1:c.252_255del - frameshift variant - [Sequence Ontology: SO:0001589]
- NM_001406868.1:c.66_69del - frameshift variant - [Sequence Ontology: SO:0001589]
- NM_001406869.1:c.66_69del - frameshift variant - [Sequence Ontology: SO:0001589]
- NM_001406870.1:c.66_69del - frameshift variant - [Sequence Ontology: SO:0001589]
- NM_001406871.1:c.66_69del - frameshift variant - [Sequence Ontology: SO:0001589]
- NM_001406872.1:c.66_69del - frameshift variant - [Sequence Ontology: SO:0001589]
- NM_001406873.1:c.66_69del - frameshift variant - [Sequence Ontology: SO:0001589]
- NM_001406874.1:c.66_69del - frameshift variant - [Sequence Ontology: SO:0001589]
- NM_001406884.1:c.66_69del - frameshift variant - [Sequence Ontology: SO:0001589]
- NM_001406885.1:c.66_69del - frameshift variant - [Sequence Ontology: SO:0001589]
- NM_001406886.1:c.66_69del - frameshift variant - [Sequence Ontology: SO:0001589]
- NM_001406912.1:c.66_69del - frameshift variant - [Sequence Ontology: SO:0001589]
- NM_001322004.2:c.-242-1931_-242-1928del - intron variant - [Sequence Ontology: SO:0001627]
- NM_001322008.2:c.-52-1931_-52-1928del - intron variant - [Sequence Ontology: SO:0001627]
- NM_001322010.2:c.-242-1931_-242-1928del - intron variant - [Sequence Ontology: SO:0001627]
- NM_001406879.1:c.-321-1931_-321-1928del - intron variant - [Sequence Ontology: SO:0001627]
- NM_001406881.1:c.-218-1931_-218-1928del - intron variant - [Sequence Ontology: SO:0001627]
- NM_001406895.1:c.-189-1931_-189-1928del - intron variant - [Sequence Ontology: SO:0001627]
- NM_001406911.1:c.-242-1931_-242-1928del - intron variant - [Sequence Ontology: SO:0001627]
- NR_136154.1:n.149AGTC[1] - non-coding transcript variant - [Sequence Ontology: SO:0001619]
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 |
---|---|---|---|---|---|---|
SCV004330120 | Labcorp Genetics (formerly Invitae), Labcorp | criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) | Pathogenic (Oct 26, 2023) | 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
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
Thompson BA, Spurdle AB, Plazzer JP, Greenblatt MS, Akagi K, Al-Mulla F, Bapat B, Bernstein I, Capellá G, den Dunnen JT, du Sart D, Fabre A, Farrell MP, Farrington SM, Frayling IM, Frebourg T, Goldgar DE, Heinen CD, Holinski-Feder E, Kohonen-Corish M, Robinson KL, Leung SY, et al.
Nat Genet. 2014 Feb;46(2):107-115. doi: 10.1038/ng.2854. Epub 2013 Dec 22.
- PMID:
- 24362816
- PMCID:
- PMC4294709
Details of each submission
From Labcorp Genetics (formerly Invitae), Labcorp, SCV004330120.1
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | PubMed (3) |
Description
This sequence change creates a premature translational stop signal (p.Val23Ilefs*10) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. 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 29, 2024