NM_000535.7(PMS2):c.2008A>G (p.Lys670Glu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 29, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002420652.2

Allele description [Variation Report for NM_000535.7(PMS2):c.2008A>G (p.Lys670Glu)]

NM_000535.7(PMS2):c.2008A>G (p.Lys670Glu)

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.2008A>G (p.Lys670Glu)

HGVS:

NC_000007.14:g.5982990T>C
NG_008466.1:g.31117A>G
NM_000535.7:c.2008A>GMANE SELECT
NM_001322003.2:c.1603A>G
NM_001322004.2:c.1603A>G
NM_001322005.2:c.1603A>G
NM_001322006.2:c.1852A>G
NM_001322007.2:c.1690A>G
NM_001322008.2:c.1690A>G
NM_001322009.2:c.1603A>G
NM_001322010.2:c.1447A>G
NM_001322011.2:c.1075A>G
NM_001322012.2:c.1075A>G
NM_001322013.2:c.1435A>G
NM_001322014.2:c.2008A>G
NM_001322015.2:c.1699A>G
NP_000526.2:p.Lys670Glu
NP_001308932.1:p.Lys535Glu
NP_001308933.1:p.Lys535Glu
NP_001308934.1:p.Lys535Glu
NP_001308935.1:p.Lys618Glu
NP_001308936.1:p.Lys564Glu
NP_001308937.1:p.Lys564Glu
NP_001308938.1:p.Lys535Glu
NP_001308939.1:p.Lys483Glu
NP_001308940.1:p.Lys359Glu
NP_001308941.1:p.Lys359Glu
NP_001308942.1:p.Lys479Glu
NP_001308943.1:p.Lys670Glu
NP_001308944.1:p.Lys567Glu
LRG_161t1:c.2008A>G
LRG_161:g.31117A>G
NC_000007.13:g.6022621T>C
NM_000535.5:c.2008A>G
NM_000535.6:c.2008A>G
NR_136154.1:n.2095A>G

Protein change:

K359E

Links:

dbSNP: rs1554295980

NCBI 1000 Genomes Browser:

rs1554295980

Molecular consequence:

NM_000535.7:c.2008A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322003.2:c.1603A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322004.2:c.1603A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322005.2:c.1603A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.1852A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322007.2:c.1690A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322008.2:c.1690A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322009.2:c.1603A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322010.2:c.1447A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322011.2:c.1075A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322012.2:c.1075A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322013.2:c.1435A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.2008A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322015.2:c.1699A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.2095A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002724277	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jun 29, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29752822, 31422818 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002724277

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jun 29, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

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

Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer.

Li JY, Jing R, Wei H, Wang M, Xiaowei Q, Liu H, Jian L, Ou JH, Jiang WH, Tian FG, Sheng Y, Li HY, Xu H, Zhang RS, Guan AH, Liu K, Jiang HC, Ren Y, He JJ, Huang W, Liao N, Cai X, et al.

Int J Cancer. 2019 Jan 15;144(2):281-289. doi: 10.1002/ijc.31601. Epub 2018 Nov 8.

PubMed [citation]

PMID:: 29752822

Rates of Actionable Genetic Findings in Individuals with Colorectal Cancer or Polyps Ascertained from a Community Medical Setting.

Gordon AS, Rosenthal EA, Carrell DS, Amendola LM, Dorschner MO, Scrol A, Stanaway IB, DeVange S, Ralston JD, Zouk H, Rehm HL, Larson E, Crosslin DR, Leppig KA, Jarvik GP.

Am J Hum Genet. 2019 Sep 5;105(3):526-533. doi: 10.1016/j.ajhg.2019.07.012. Epub 2019 Aug 15.

PubMed [citation]

PMID:: 31422818
PMCID:: PMC6731361

Details of each submission

From Ambry Genetics, SCV002724277.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.K670E variant (also known as c.2008A>G), located in coding exon 12 of the PMS2 gene, results from an A to G substitution at nucleotide position 2008. The lysine at codon 670 is replaced by glutamic acid, an amino acid with similar properties. This alteration was detected in a study of 1,165 individuals with a history of colorectal cancer or colon polyps as well as 590 controls (Gordon AS et al. Am J Hum Genet, 2019 09;105:526-533). This variant was also identified in 2/937 Chinese breast cancer patients undergoing multigene panel testing (Li JY et al. Int J Cancer, 2019 01;144:281-289). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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

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