NM_000535.7(PMS2):c.320G>A (p.Arg107Gln) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 17, 2020
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:: RCV001269227.5

Allele description [Variation Report for NM_000535.7(PMS2):c.320G>A (p.Arg107Gln)]

NM_000535.7(PMS2):c.320G>A (p.Arg107Gln)

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.320G>A (p.Arg107Gln)

HGVS:

NC_000007.14:g.6003723C>T
NG_008466.1:g.10384G>A
NM_000535.7:c.320G>AMANE SELECT
NM_001322003.2:c.-86G>A
NM_001322004.2:c.-86G>A
NM_001322005.2:c.-86G>A
NM_001322006.2:c.320G>A
NM_001322007.2:c.35+249G>A
NM_001322008.2:c.35+249G>A
NM_001322009.2:c.-86G>A
NM_001322010.2:c.-86G>A
NM_001322011.2:c.-565G>A
NM_001322012.2:c.-565G>A
NM_001322013.2:c.-86G>A
NM_001322014.2:c.320G>A
NM_001322015.2:c.-165G>A
NP_000526.2:p.Arg107Gln
NP_001308935.1:p.Arg107Gln
NP_001308943.1:p.Arg107Gln
LRG_161t1:c.320G>A
LRG_161:g.10384G>A
NC_000007.13:g.6043354C>T
NM_000535.5:c.320G>A
NM_000535.6:c.320G>A
NR_136154.1:n.407G>A

Protein change:

R107Q

Links:

dbSNP: rs63751284

NCBI 1000 Genomes Browser:

rs63751284

Molecular consequence:

NM_001322003.2:c.-86G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322004.2:c.-86G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322005.2:c.-86G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322009.2:c.-86G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322010.2:c.-86G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322011.2:c.-565G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322012.2:c.-565G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322013.2:c.-86G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322015.2:c.-165G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322007.2:c.35+249G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001322008.2:c.35+249G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000535.7:c.320G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.320G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.320G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.407G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001448537	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Nov 17, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 14756672, 28135145, 15521988 Citation Link,
SCV002072350	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 1, 2019)	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

SCV001448537

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Nov 17, 2020)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV002072350

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 1, 2019)

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	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Hereditary non-polyposis colorectal cancer and the role of hPMS2 and hEXO1 mutations.

Thompson E, Meldrum CJ, Crooks R, McPhillips M, Thomas L, Spigelman AD, Scott RJ.

Clin Genet. 2004 Mar;65(3):215-25.

PubMed [citation]

PMID:: 14756672

Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.

Yurgelun MB, Kulke MH, Fuchs CS, Allen BA, Uno H, Hornick JL, Ukaegbu CI, Brais LK, McNamara PG, Mayer RJ, Schrag D, Meyerhardt JA, Ng K, Kidd J, Singh N, Hartman AR, Wenstrup RJ, Syngal S.

J Clin Oncol. 2017 Apr 1;35(10):1086-1095. doi: 10.1200/JCO.2016.71.0012. Epub 2017 Jan 30.

PubMed [citation]

PMID:: 28135145
PMCID:: PMC5455355

See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001448537.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: PPMS2 c.320G>A (p.Arg107Gln) results in a conservative amino acid change located in the DNA mismatch repair protein family, N-terminal domain (IPR002099) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.2e-05 in 236632 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in PMS2 causing Hereditary Nonpolyposis Colorectal Cancer (4.2e-05 vs 7.1e-05), allowing no conclusion about variant significance. c.320G>A has been reported in the literature in individuals affected with Hereditary Nonpolyposis Colorectal Cancer (Thompson_2004, Yurgelun_2017). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Nonpolyposis Colorectal Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submitters (evaluation after 2014) cite 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 Genetic Services Laboratory, University of Chicago, SCV002072350.1

#	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

ClinVar

Relating variation to medicine