NM_000535.7(PMS2):c.299A>C (p.Gln100Pro) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 28, 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:: RCV000165733.10

Allele description [Variation Report for NM_000535.7(PMS2):c.299A>C (p.Gln100Pro)]

NM_000535.7(PMS2):c.299A>C (p.Gln100Pro)

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.299A>C (p.Gln100Pro)

HGVS:

NC_000007.14:g.6003744T>G
NG_008466.1:g.10363A>C
NM_000535.7:c.299A>CMANE SELECT
NM_001322003.2:c.-107A>C
NM_001322004.2:c.-107A>C
NM_001322005.2:c.-107A>C
NM_001322006.2:c.299A>C
NM_001322007.2:c.35+228A>C
NM_001322008.2:c.35+228A>C
NM_001322009.2:c.-107A>C
NM_001322010.2:c.-107A>C
NM_001322011.2:c.-586A>C
NM_001322012.2:c.-586A>C
NM_001322013.2:c.-107A>C
NM_001322014.2:c.299A>C
NM_001322015.2:c.-186A>C
NP_000526.2:p.Gln100Pro
NP_001308935.1:p.Gln100Pro
NP_001308943.1:p.Gln100Pro
LRG_161t1:c.299A>C
LRG_161:g.10363A>C
NC_000007.13:g.6043375T>G
NM_000535.5:c.299A>C
NM_000535.6:c.299A>C
NR_136154.1:n.386A>C
p.Q100P

Protein change:

Q100P

Links:

dbSNP: rs747771951

NCBI 1000 Genomes Browser:

rs747771951

Molecular consequence:

NM_001322003.2:c.-107A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322004.2:c.-107A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322005.2:c.-107A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322009.2:c.-107A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322010.2:c.-107A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322011.2:c.-586A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322012.2:c.-586A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322013.2:c.-107A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322015.2:c.-186A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322007.2:c.35+228A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001322008.2:c.35+228A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000535.7:c.299A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.299A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.299A>C - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.386A>C - 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

Recent activity

Clear Turn Off Turn On

Tssr907 AND (alive[prop]) (0)
Gene

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
SCV000216474	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 28, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32091409, 35449176 Citation Link,
SCV000686187	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 25, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 32068069, 34172528, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000216474

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 28, 2023)

germline

clinical testing

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

Citation Link,

SCV000686187

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 25, 2023)

germline

clinical testing

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

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

Comparison of BRCA versus non-BRCA germline mutations and associated somatic mutation profiles in patients with unselected breast cancer.

Chen B, Zhang G, Li X, Ren C, Wang Y, Li K, Mok H, Cao L, Wen L, Jia M, Li C, Guo L, Wei G, Lin J, Li Y, Zhang Y, Han-Zhang H, Liu J, Lizaso A, Liao N.

Aging (Albany NY). 2020 Feb 24;12(4):3140-3155. doi: 10.18632/aging.102783. Epub 2020 Feb 24.

PubMed [citation]

PMID:: 32091409
PMCID:: PMC7066887

Clinical relevance of pathogenic germline variants in mismatch repair genes in Chinese breast cancer patients.

Hu L, Sun J, Li Z, Qu Z, Liu Y, Wan Q, Liu J, Ding X, Zang F, Zhang J, Yao L, Xu Y, Wang Y, Xie Y.

NPJ Breast Cancer. 2022 Apr 21;8(1):52. doi: 10.1038/s41523-022-00417-x.

PubMed [citation]

PMID:: 35449176
PMCID:: PMC9023502

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000216474.7

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

Description

The p.Q100P variant (also known as c.299A>C), located in coding exon 4 of the PMS2 gene, results from an A to C substitution at nucleotide position 299. The glutamine at codon 100 is replaced by proline, an amino acid with similar properties. This alteration has been identified in cohorts of Chinese breast cancer patients (Chen B et al. Aging (Albany NY), 2020 Feb;12:3140-3155; Hu L et al. NPJ Breast Cancer, 2022 Apr;8:52). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated 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

From Color Diagnostics, LLC DBA Color Health, SCV000686187.5

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

Description

This missense variant replaces glutamine with proline at codon 100 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has been reported in individuals affected with colorectal cancer (PMID: 34172528), or breast cancer (PMID: 32068069). This variant has been identified in 4/238842 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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

ClinVar

Relating variation to medicine