NM_000535.7(PMS2):c.944G>A (p.Arg315Gln) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 15, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000780629.4

Allele description [Variation Report for NM_000535.7(PMS2):c.944G>A (p.Arg315Gln)]

NM_000535.7(PMS2):c.944G>A (p.Arg315Gln)

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.944G>A (p.Arg315Gln)

HGVS:

NC_000007.14:g.5992017C>T
NG_008466.1:g.22090G>A
NM_000535.7:c.944G>AMANE SELECT
NM_001322003.2:c.539G>A
NM_001322004.2:c.539G>A
NM_001322005.2:c.539G>A
NM_001322006.2:c.944G>A
NM_001322007.2:c.626G>A
NM_001322008.2:c.626G>A
NM_001322009.2:c.539G>A
NM_001322010.2:c.539G>A
NM_001322011.2:c.11G>A
NM_001322012.2:c.11G>A
NM_001322013.2:c.371G>A
NM_001322014.2:c.944G>A
NM_001322015.2:c.635G>A
NP_000526.2:p.Arg315Gln
NP_001308932.1:p.Arg180Gln
NP_001308933.1:p.Arg180Gln
NP_001308934.1:p.Arg180Gln
NP_001308935.1:p.Arg315Gln
NP_001308936.1:p.Arg209Gln
NP_001308937.1:p.Arg209Gln
NP_001308938.1:p.Arg180Gln
NP_001308939.1:p.Arg180Gln
NP_001308940.1:p.Arg4Gln
NP_001308941.1:p.Arg4Gln
NP_001308942.1:p.Arg124Gln
NP_001308943.1:p.Arg315Gln
NP_001308944.1:p.Arg212Gln
LRG_161t1:c.944G>A
LRG_161:g.22090G>A
NC_000007.13:g.6031648C>T
NM_000535.5:c.944G>A
NM_000535.6:c.944G>A
NR_136154.1:n.1031G>A
p.R315Q

Protein change:

R124Q

Links:

dbSNP: rs116314131

NCBI 1000 Genomes Browser:

rs116314131

Molecular consequence:

NM_000535.7:c.944G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322003.2:c.539G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322004.2:c.539G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322005.2:c.539G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.944G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322007.2:c.626G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322008.2:c.626G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322009.2:c.539G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322010.2:c.539G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322011.2:c.11G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322012.2:c.11G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322013.2:c.371G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.944G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322015.2:c.635G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.1031G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000918059	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Nov 3, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25503501, 26845104 Citation Link,
SCV002760378	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 15, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000918059

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Nov 3, 2022)

germline

clinical testing

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

Citation Link,

SCV002760378

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 15, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Prevalence of mutations in a panel of breast cancer susceptibility genes in BRCA1/2-negative patients with early-onset breast cancer.

Maxwell KN, Wubbenhorst B, D'Andrea K, Garman B, Long JM, Powers J, Rathbun K, Stopfer JE, Zhu J, Bradbury AR, Simon MS, DeMichele A, Domchek SM, Nathanson KL.

Genet Med. 2015 Aug;17(8):630-8. doi: 10.1038/gim.2014.176. Epub 2014 Dec 11.

PubMed [citation]

PMID:: 25503501
PMCID:: PMC4465412

Improving performance of multigene panels for genomic analysis of cancer predisposition.

Shirts BH, Casadei S, Jacobson AL, Lee MK, Gulsuner S, Bennett RL, Miller M, Hall SA, Hampel H, Hisama FM, Naylor LV, Goetsch C, Leppig K, Tait JF, Scroggins SM, Turner EH, Livingston R, Salipante SJ, King MC, Walsh T, Pritchard CC.

Genet Med. 2016 Oct;18(10):974-81. doi: 10.1038/gim.2015.212. Epub 2016 Feb 4.

PubMed [citation]

PMID:: 26845104

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000918059.2

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

Description

Variant summary: PMS2 c.944G>A (p.Arg315Gln) results in a conservative amino acid change located in the DNA mismatch repair protein, S5 domain 2-like of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251260 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.944G>A has been reported in the literature in an individual with breast cancer who also carried a pathogenic (CHEK2 c.1283C>T, p.Ser428Phe) variant (Maxwell_2014), as well as in a patient with ovarian cancer (Shirts_2016). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Nonpolyposis Colorectal Cancer. Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as 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

From Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, SCV002760378.3

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

#	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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