NM_000535.7(PMS2):c.2319T>G (p.Ser773Arg) AND Hereditary nonpolyposis colorectal neoplasms
- Germline classification:
- Uncertain significance (1 submission)
- Last evaluated:
- Jun 16, 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:
- RCV003595249.2
Allele description [Variation Report for NM_000535.7(PMS2):c.2319T>G (p.Ser773Arg)]
NM_000535.7(PMS2):c.2319T>G (p.Ser773Arg)
- 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.2319T>G (p.Ser773Arg)
- HGVS:
- NC_000007.14:g.5977714A>C
- NG_008466.1:g.36393T>G
- NM_000535.7:c.2319T>GMANE SELECT
- NM_001018040.1:c.1914T>G
- NM_001322003.2:c.1914T>G
- NM_001322004.2:c.1914T>G
- NM_001322005.2:c.1914T>G
- NM_001322006.2:c.2163T>G
- NM_001322007.2:c.2001T>G
- NM_001322008.2:c.2001T>G
- NM_001322009.2:c.1947T>G
- NM_001322010.2:c.1758T>G
- NM_001322011.2:c.1386T>G
- NM_001322012.2:c.1386T>G
- NM_001322013.2:c.1746T>G
- NM_001322014.2:c.2352T>G
- NM_001322015.2:c.2010T>G
- NM_001406866.1:c.2505T>G
- NM_001406868.1:c.2343T>G
- NM_001406869.1:c.2211T>G
- NM_001406870.1:c.2196T>G
- NM_001406871.1:c.2175T>G
- NM_001406872.1:c.2151T>G
- NM_001406873.1:c.2121T>G
- NM_001406874.1:c.2151T>G
- NM_001406875.1:c.2043T>G
- NM_001406876.1:c.2034T>G
- NM_001406877.1:c.2010T>G
- NM_001406878.1:c.2010T>G
- NM_001406879.1:c.2010T>G
- NM_001406880.1:c.2010T>G
- NM_001406881.1:c.2010T>G
- NM_001406882.1:c.2010T>G
- NM_001406883.1:c.2001T>G
- NM_001406884.1:c.1995T>G
- NM_001406885.1:c.1983T>G
- NM_001406886.1:c.1953T>G
- NM_001406887.1:c.1947T>G
- NM_001406888.1:c.1947T>G
- NM_001406889.1:c.1914T>G
- NM_001406890.1:c.1914T>G
- NM_001406891.1:c.1914T>G
- NM_001406892.1:c.1914T>G
- NM_001406893.1:c.1914T>G
- NM_001406894.1:c.1914T>G
- NM_001406895.1:c.1914T>G
- NM_001406896.1:c.1914T>G
- NM_001406897.1:c.1914T>G
- NM_001406898.1:c.1914T>G
- NM_001406899.1:c.1914T>G
- NM_001406900.1:c.1854T>G
- NM_001406901.1:c.1845T>G
- NM_001406902.1:c.1845T>G
- NM_001406903.1:c.1833T>G
- NM_001406904.1:c.1806T>G
- NM_001406905.1:c.1806T>G
- NM_001406906.1:c.1758T>G
- NM_001406907.1:c.1758T>G
- NM_001406908.1:c.1746T>G
- NM_001406909.1:c.1746T>G
- NM_001406910.1:c.1602T>G
- NM_001406911.1:c.1548T>G
- NM_001406912.1:c.1116T>G
- NP_000526.1:p.Ser773Arg
- NP_000526.2:p.Ser773Arg
- NP_001018050.1:p.Ser638Arg
- NP_001308932.1:p.Ser638Arg
- NP_001308933.1:p.Ser638Arg
- NP_001308934.1:p.Ser638Arg
- NP_001308935.1:p.Ser721Arg
- NP_001308936.1:p.Ser667Arg
- NP_001308937.1:p.Ser667Arg
- NP_001308938.1:p.Ser649Arg
- NP_001308939.1:p.Ser586Arg
- NP_001308940.1:p.Ser462Arg
- NP_001308941.1:p.Ser462Arg
- NP_001308942.1:p.Ser582Arg
- NP_001308943.1:p.Ser784Arg
- NP_001308944.1:p.Ser670Arg
- NP_001393795.1:p.Ser835Arg
- NP_001393797.1:p.Ser781Arg
- NP_001393798.1:p.Ser737Arg
- NP_001393799.1:p.Ser732Arg
- NP_001393800.1:p.Ala725=
- NP_001393801.1:p.Ser717Arg
- NP_001393802.1:p.Ser707Arg
- NP_001393803.1:p.Ser717Arg
- NP_001393804.1:p.Ser681Arg
- NP_001393805.1:p.Ser678Arg
- NP_001393806.1:p.Ser670Arg
- NP_001393807.1:p.Ser670Arg
- NP_001393808.1:p.Ser670Arg
- NP_001393809.1:p.Ser670Arg
- NP_001393810.1:p.Ser670Arg
- NP_001393811.1:p.Ser670Arg
- NP_001393812.1:p.Ser667Arg
- NP_001393813.1:p.Ser665Arg
- NP_001393814.1:p.Ser661Arg
- NP_001393815.1:p.Ser651Arg
- NP_001393816.1:p.Ser649Arg
- NP_001393817.1:p.Ser649Arg
- NP_001393818.1:p.Ser638Arg
- NP_001393819.1:p.Ser638Arg
- NP_001393820.1:p.Ser638Arg
- NP_001393821.1:p.Ser638Arg
- NP_001393822.1:p.Ser638Arg
- NP_001393823.1:p.Ser638Arg
- NP_001393824.1:p.Ser638Arg
- NP_001393825.1:p.Ser638Arg
- NP_001393826.1:p.Ser638Arg
- NP_001393827.1:p.Ser638Arg
- NP_001393828.1:p.Ser638Arg
- NP_001393829.1:p.Ser618Arg
- NP_001393830.1:p.Ser615Arg
- NP_001393831.1:p.Ser615Arg
- NP_001393832.1:p.Ser611Arg
- NP_001393833.1:p.Ser602Arg
- NP_001393834.1:p.Ser602Arg
- NP_001393835.1:p.Ser586Arg
- NP_001393836.1:p.Ser586Arg
- NP_001393837.1:p.Ser582Arg
- NP_001393838.1:p.Ser582Arg
- NP_001393839.1:p.Ser534Arg
- NP_001393840.1:p.Ser516Arg
- NP_001393841.1:p.Ser372Arg
- LRG_161t1:c.2319T>G
- LRG_161:g.36393T>G
- LRG_161p1:p.Ser773Arg
- NC_000007.13:g.6017345A>C
- NM_000535.5:c.2319T>G
- NR_003085.2:n.2401T>G
- NR_136154.1:n.2363T>G
This HGVS expression did not pass validation- Protein change:
- S372R
- Molecular consequence:
- NM_000535.7:c.2319T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001018040.1:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322003.2:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322004.2:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322005.2:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322006.2:c.2163T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322007.2:c.2001T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322008.2:c.2001T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322009.2:c.1947T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322010.2:c.1758T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322011.2:c.1386T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322012.2:c.1386T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322013.2:c.1746T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322014.2:c.2352T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322015.2:c.2010T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406866.1:c.2505T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406868.1:c.2343T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406869.1:c.2211T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406870.1:c.2196T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406872.1:c.2151T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406873.1:c.2121T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406874.1:c.2151T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406875.1:c.2043T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406876.1:c.2034T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406877.1:c.2010T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406878.1:c.2010T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406879.1:c.2010T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406880.1:c.2010T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406881.1:c.2010T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406882.1:c.2010T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406883.1:c.2001T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406884.1:c.1995T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406885.1:c.1983T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406886.1:c.1953T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406887.1:c.1947T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406888.1:c.1947T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406889.1:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406890.1:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406891.1:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406892.1:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406893.1:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406894.1:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406895.1:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406896.1:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406897.1:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406898.1:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406899.1:c.1914T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406900.1:c.1854T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406901.1:c.1845T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406902.1:c.1845T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406903.1:c.1833T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406904.1:c.1806T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406905.1:c.1806T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406906.1:c.1758T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406907.1:c.1758T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406908.1:c.1746T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406909.1:c.1746T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406910.1:c.1602T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406911.1:c.1548T>G - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406912.1:c.1116T>G - missense variant - [Sequence Ontology: SO:0001583]
- NR_136154.1:n.2363T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
- NM_001406871.1:c.2175T>G - synonymous variant - [Sequence Ontology: SO:0001819]
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 |
---|---|---|---|---|---|---|
SCV004272960 | Labcorp Genetics (formerly Invitae), Labcorp | criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) | Uncertain significance (Jun 16, 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
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.
Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.
Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.
- PMID:
- 28492532
- PMCID:
- PMC5632818
Details of each submission
From Labcorp Genetics (formerly Invitae), Labcorp, SCV004272960.1
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | PubMed (1) |
Description
This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 773 of the PMS2 protein (p.Ser773Arg). RNA analysis indicates that this missense change induces altered splicing and may result in an absent or disrupted protein product. 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 variant has not been reported in the literature in individuals affected with PMS2-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PMS2 protein function. Studies have shown that this missense change results in deletion of partial exon 14 and introduces a premature termination codon (Inviate). The resulting mRNA is expected to undergo nonsense-mediated decay. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
# | 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