NM_000535.7(PMS2):c.1948G>C (p.Ala650Pro) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 2, 2022
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:: RCV001177469.4

Allele description [Variation Report for NM_000535.7(PMS2):c.1948G>C (p.Ala650Pro)]

NM_000535.7(PMS2):c.1948G>C (p.Ala650Pro)

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.1948G>C (p.Ala650Pro)

HGVS:

NC_000007.14:g.5986817C>G
NG_008466.1:g.27290G>C
NM_000535.7:c.1948G>CMANE SELECT
NM_001322003.2:c.1543G>C
NM_001322004.2:c.1543G>C
NM_001322005.2:c.1543G>C
NM_001322006.2:c.1792G>C
NM_001322007.2:c.1630G>C
NM_001322008.2:c.1630G>C
NM_001322009.2:c.1543G>C
NM_001322010.2:c.1387G>C
NM_001322011.2:c.1015G>C
NM_001322012.2:c.1015G>C
NM_001322013.2:c.1375G>C
NM_001322014.2:c.1948G>C
NM_001322015.2:c.1639G>C
NP_000526.2:p.Ala650Pro
NP_001308932.1:p.Ala515Pro
NP_001308933.1:p.Ala515Pro
NP_001308934.1:p.Ala515Pro
NP_001308935.1:p.Ala598Pro
NP_001308936.1:p.Ala544Pro
NP_001308937.1:p.Ala544Pro
NP_001308938.1:p.Ala515Pro
NP_001308939.1:p.Ala463Pro
NP_001308940.1:p.Ala339Pro
NP_001308941.1:p.Ala339Pro
NP_001308942.1:p.Ala459Pro
NP_001308943.1:p.Ala650Pro
NP_001308944.1:p.Ala547Pro
LRG_161t1:c.1948G>C
LRG_161:g.27290G>C
NC_000007.13:g.6026448C>G
NC_000007.13:g.6026448C>G
NM_000535.5:c.1948G>C
NM_000535.6:c.1948G>C
NR_136154.1:n.2035G>C

Protein change:

A339P

Links:

dbSNP: rs1782930647

NCBI 1000 Genomes Browser:

rs1782930647

Molecular consequence:

NM_000535.7:c.1948G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322003.2:c.1543G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322004.2:c.1543G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322005.2:c.1543G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.1792G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322007.2:c.1630G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322008.2:c.1630G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322009.2:c.1543G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322010.2:c.1387G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322011.2:c.1015G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322012.2:c.1015G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322013.2:c.1375G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.1948G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322015.2:c.1639G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.2035G>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001341694	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 4, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002722829	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Aug 2, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001341694

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 4, 2019)

germline

clinical testing

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

SCV002722829

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Aug 2, 2022)

germline

clinical testing

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

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Mutations in mismatch repair genes are involved in the neoplastic transformation of human breast epithelial cells.

Balogh GA, Russo IH, Russo J.

Int J Oncol. 2003 Aug;23(2):411-9.

PubMed [citation]

PMID:: 12851690

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001341694.1

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Ambry Genetics, SCV002722829.2

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

Description

The p.A650P variant (also known as c.1948G>C), located in coding exon 11 of the PMS2 gene, results from a G to C substitution at nucleotide position 1948. The alanine at codon 650 is replaced by proline, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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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