NM_000535.7(PMS2):c.2127C>A (p.Phe709Leu) AND Hereditary nonpolyposis colorectal neoplasms
- Germline classification:
- Uncertain significance (1 submission)
- Last evaluated:
- Aug 12, 2021
- 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:
- RCV003098637.2
Allele description [Variation Report for NM_000535.7(PMS2):c.2127C>A (p.Phe709Leu)]
NM_000535.7(PMS2):c.2127C>A (p.Phe709Leu)
- 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.2127C>A (p.Phe709Leu)
- HGVS:
- NC_000007.14:g.5982871G>T
- NG_008466.1:g.31236C>A
- NM_000535.7:c.2127C>AMANE SELECT
- NM_001018040.1:c.1722C>A
- NM_001322003.2:c.1722C>A
- NM_001322004.2:c.1722C>A
- NM_001322005.2:c.1722C>A
- NM_001322006.2:c.1971C>A
- NM_001322007.2:c.1809C>A
- NM_001322008.2:c.1809C>A
- NM_001322009.2:c.1722C>A
- NM_001322010.2:c.1566C>A
- NM_001322011.2:c.1194C>A
- NM_001322012.2:c.1194C>A
- NM_001322013.2:c.1554C>A
- NM_001322014.2:c.2127C>A
- NM_001322015.2:c.1818C>A
- NM_001406866.1:c.2313C>A
- NM_001406868.1:c.2151C>A
- NM_001406869.1:c.2019C>A
- NM_001406870.1:c.1971C>A
- NM_001406871.1:c.2127C>A
- NM_001406873.1:c.1929C>A
- NM_001406874.1:c.1959C>A
- NM_001406875.1:c.1818C>A
- NM_001406876.1:c.1809C>A
- NM_001406877.1:c.1818C>A
- NM_001406878.1:c.1818C>A
- NM_001406879.1:c.1818C>A
- NM_001406880.1:c.1818C>A
- NM_001406881.1:c.1818C>A
- NM_001406882.1:c.1818C>A
- NM_001406883.1:c.1809C>A
- NM_001406884.1:c.1803C>A
- NM_001406885.1:c.1791C>A
- NM_001406886.1:c.1761C>A
- NM_001406887.1:c.1722C>A
- NM_001406888.1:c.1722C>A
- NM_001406889.1:c.1722C>A
- NM_001406890.1:c.1722C>A
- NM_001406891.1:c.1722C>A
- NM_001406892.1:c.1722C>A
- NM_001406893.1:c.1722C>A
- NM_001406894.1:c.1722C>A
- NM_001406895.1:c.1722C>A
- NM_001406896.1:c.1722C>A
- NM_001406897.1:c.1722C>A
- NM_001406898.1:c.1722C>A
- NM_001406899.1:c.1722C>A
- NM_001406900.1:c.1662C>A
- NM_001406901.1:c.1653C>A
- NM_001406902.1:c.1653C>A
- NM_001406904.1:c.1614C>A
- NM_001406905.1:c.1614C>A
- NM_001406906.1:c.1566C>A
- NM_001406907.1:c.1566C>A
- NM_001406909.1:c.1554C>A
- NM_001406911.1:c.1356C>A
- NM_001406912.1:c.924C>A
- NP_000526.1:p.Phe709Leu
- NP_000526.2:p.Phe709Leu
- NP_001018050.1:p.Phe574Leu
- NP_001308932.1:p.Phe574Leu
- NP_001308933.1:p.Phe574Leu
- NP_001308934.1:p.Phe574Leu
- NP_001308935.1:p.Phe657Leu
- NP_001308936.1:p.Phe603Leu
- NP_001308937.1:p.Phe603Leu
- NP_001308938.1:p.Phe574Leu
- NP_001308939.1:p.Phe522Leu
- NP_001308940.1:p.Phe398Leu
- NP_001308941.1:p.Phe398Leu
- NP_001308942.1:p.Phe518Leu
- NP_001308943.1:p.Phe709Leu
- NP_001308944.1:p.Phe606Leu
- NP_001393795.1:p.Phe771Leu
- NP_001393797.1:p.Phe717Leu
- NP_001393798.1:p.Phe673Leu
- NP_001393799.1:p.Phe657Leu
- NP_001393800.1:p.Phe709Leu
- NP_001393802.1:p.Phe643Leu
- NP_001393803.1:p.Phe653Leu
- NP_001393804.1:p.Phe606Leu
- NP_001393805.1:p.Phe603Leu
- NP_001393806.1:p.Phe606Leu
- NP_001393807.1:p.Phe606Leu
- NP_001393808.1:p.Phe606Leu
- NP_001393809.1:p.Phe606Leu
- NP_001393810.1:p.Phe606Leu
- NP_001393811.1:p.Phe606Leu
- NP_001393812.1:p.Phe603Leu
- NP_001393813.1:p.Phe601Leu
- NP_001393814.1:p.Phe597Leu
- NP_001393815.1:p.Phe587Leu
- NP_001393816.1:p.Phe574Leu
- NP_001393817.1:p.Phe574Leu
- NP_001393818.1:p.Phe574Leu
- NP_001393819.1:p.Phe574Leu
- NP_001393820.1:p.Phe574Leu
- NP_001393821.1:p.Phe574Leu
- NP_001393822.1:p.Phe574Leu
- NP_001393823.1:p.Phe574Leu
- NP_001393824.1:p.Phe574Leu
- NP_001393825.1:p.Phe574Leu
- NP_001393826.1:p.Phe574Leu
- NP_001393827.1:p.Phe574Leu
- NP_001393828.1:p.Phe574Leu
- NP_001393829.1:p.Phe554Leu
- NP_001393830.1:p.Phe551Leu
- NP_001393831.1:p.Phe551Leu
- NP_001393833.1:p.Phe538Leu
- NP_001393834.1:p.Phe538Leu
- NP_001393835.1:p.Phe522Leu
- NP_001393836.1:p.Phe522Leu
- NP_001393838.1:p.Phe518Leu
- NP_001393840.1:p.Phe452Leu
- NP_001393841.1:p.Phe308Leu
- LRG_161t1:c.2127C>A
- LRG_161:g.31236C>A
- LRG_161p1:p.Phe709Leu
- NC_000007.13:g.6022502G>T
- NM_000535.5:c.2127C>A
- NR_003085.2:n.2209C>A
- NR_136154.1:n.2214C>A
This HGVS expression did not pass validation- Protein change:
- F308L
- Molecular consequence:
- NM_000535.7:c.2127C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001018040.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322003.2:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322004.2:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322005.2:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322006.2:c.1971C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322007.2:c.1809C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322008.2:c.1809C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322009.2:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322010.2:c.1566C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322011.2:c.1194C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322012.2:c.1194C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322013.2:c.1554C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322014.2:c.2127C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001322015.2:c.1818C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406866.1:c.2313C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406868.1:c.2151C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406869.1:c.2019C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406870.1:c.1971C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406871.1:c.2127C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406873.1:c.1929C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406874.1:c.1959C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406875.1:c.1818C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406876.1:c.1809C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406877.1:c.1818C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406878.1:c.1818C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406879.1:c.1818C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406880.1:c.1818C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406881.1:c.1818C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406882.1:c.1818C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406883.1:c.1809C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406884.1:c.1803C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406885.1:c.1791C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406886.1:c.1761C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406887.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406888.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406889.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406890.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406891.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406892.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406893.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406894.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406895.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406896.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406897.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406898.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406899.1:c.1722C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406900.1:c.1662C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406901.1:c.1653C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406902.1:c.1653C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406904.1:c.1614C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406905.1:c.1614C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406906.1:c.1566C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406907.1:c.1566C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406909.1:c.1554C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406911.1:c.1356C>A - missense variant - [Sequence Ontology: SO:0001583]
- NM_001406912.1:c.924C>A - missense variant - [Sequence Ontology: SO:0001583]
- NR_136154.1:n.2214C>A - 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 |
---|---|---|---|---|---|---|
SCV003243121 | Labcorp Genetics (formerly Invitae), Labcorp | criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) | Uncertain significance (Aug 12, 2021) | 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, SCV003243121.1
# | 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 phenylalanine with leucine at codon 709 of the PMS2 protein (p.Phe709Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant has not been reported in the literature in individuals affected with PMS2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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