NM_000535.7(PMS2):c.869T>C (p.Phe290Ser) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 17, 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:: RCV000775715.6

Allele description [Variation Report for NM_000535.7(PMS2):c.869T>C (p.Phe290Ser)]

NM_000535.7(PMS2):c.869T>C (p.Phe290Ser)

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.869T>C (p.Phe290Ser)

HGVS:

NC_000007.14:g.5995568A>G
NG_008466.1:g.18539T>C
NM_000535.7:c.869T>CMANE SELECT
NM_001322003.2:c.464T>C
NM_001322004.2:c.464T>C
NM_001322005.2:c.464T>C
NM_001322006.2:c.869T>C
NM_001322007.2:c.551T>C
NM_001322008.2:c.551T>C
NM_001322009.2:c.464T>C
NM_001322010.2:c.464T>C
NM_001322011.2:c.-65T>C
NM_001322012.2:c.-65T>C
NM_001322013.2:c.296T>C
NM_001322014.2:c.869T>C
NM_001322015.2:c.560T>C
NP_000526.2:p.Phe290Ser
NP_001308932.1:p.Phe155Ser
NP_001308933.1:p.Phe155Ser
NP_001308934.1:p.Phe155Ser
NP_001308935.1:p.Phe290Ser
NP_001308936.1:p.Phe184Ser
NP_001308937.1:p.Phe184Ser
NP_001308938.1:p.Phe155Ser
NP_001308939.1:p.Phe155Ser
NP_001308942.1:p.Phe99Ser
NP_001308943.1:p.Phe290Ser
NP_001308944.1:p.Phe187Ser
LRG_161t1:c.869T>C
LRG_161:g.18539T>C
NC_000007.13:g.6035199A>G
NM_000535.5:c.869T>C
NM_000535.6:c.869T>C
NR_136154.1:n.956T>C

Protein change:

F155S

Links:

dbSNP: rs1031512870

NCBI 1000 Genomes Browser:

rs1031512870

Molecular consequence:

NM_001322011.2:c.-65T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322012.2:c.-65T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000535.7:c.869T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322003.2:c.464T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322004.2:c.464T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322005.2:c.464T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.869T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322007.2:c.551T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322008.2:c.551T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322009.2:c.464T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322010.2:c.464T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322013.2:c.296T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.869T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322015.2:c.560T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.956T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

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

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
SCV000910132	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 17, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002684132	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Uncertain significance (Apr 19, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000910132

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 17, 2023)

germline

clinical testing

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

SCV002684132

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Uncertain significance
(Apr 19, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	1	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

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000910132.4

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

Description

This missense variant replaces phenylalanine with serine at codon 290 of the PMS2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PMS2-related disorders in the literature. This variant has not been identified 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

From Ambry Genetics, SCV002684132.1

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

Description

The p.F290S variant (also known as c.869T>C), located in coding exon 8 of the PMS2 gene, results from a T to C substitution at nucleotide position 869. The phenylalanine at codon 290 is replaced by serine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Apr 20, 2024

ClinVar

Relating variation to medicine