NM_000535.7(PMS2):c.641T>G (p.Val214Gly) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 5, 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:: RCV000584176.7

Allele description [Variation Report for NM_000535.7(PMS2):c.641T>G (p.Val214Gly)]

NM_000535.7(PMS2):c.641T>G (p.Val214Gly)

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.641T>G (p.Val214Gly)

HGVS:

NC_000007.14:g.5999172A>C
NG_008466.1:g.14935T>G
NM_000535.7:c.641T>GMANE SELECT
NM_001322003.2:c.236T>G
NM_001322004.2:c.236T>G
NM_001322005.2:c.236T>G
NM_001322006.2:c.641T>G
NM_001322007.2:c.323T>G
NM_001322008.2:c.323T>G
NM_001322009.2:c.236T>G
NM_001322010.2:c.236T>G
NM_001322011.2:c.-293T>G
NM_001322012.2:c.-293T>G
NM_001322013.2:c.133-1749T>G
NM_001322014.2:c.641T>G
NM_001322015.2:c.332T>G
NP_000526.2:p.Val214Gly
NP_001308932.1:p.Val79Gly
NP_001308933.1:p.Val79Gly
NP_001308934.1:p.Val79Gly
NP_001308935.1:p.Val214Gly
NP_001308936.1:p.Val108Gly
NP_001308937.1:p.Val108Gly
NP_001308938.1:p.Val79Gly
NP_001308939.1:p.Val79Gly
NP_001308943.1:p.Val214Gly
NP_001308944.1:p.Val111Gly
LRG_161t1:c.641T>G
LRG_161:g.14935T>G
NC_000007.13:g.6038803A>C
NM_000535.5:c.641T>G
NM_000535.6:c.641T>G
NR_136154.1:n.728T>G

Protein change:

V108G

Links:

dbSNP: rs864622706

NCBI 1000 Genomes Browser:

rs864622706

Molecular consequence:

NM_001322011.2:c.-293T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322012.2:c.-293T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322013.2:c.133-1749T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000535.7:c.641T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322003.2:c.236T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322004.2:c.236T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322005.2:c.236T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.641T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322007.2:c.323T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322008.2:c.323T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322009.2:c.236T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322010.2:c.236T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.641T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322015.2:c.332T>G - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.728T>G - 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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Streptococcus agalactiae strain GB-PW-091 ctg7180000001725, whole genome shotgun...
Streptococcus agalactiae strain GB-PW-091 ctg7180000001725, whole genome shotgun sequence
gi|825941802|gb|LCXD01000018.1||gnl LCXD01|ctg7180000001725

Nucleotide
Streptococcus agalactiae strain GB-PW-087 ctg7180000005231, whole genome shotgun...
Streptococcus agalactiae strain GB-PW-087 ctg7180000005231, whole genome shotgun sequence
gi|825939542|gb|LCXB01000009.1||gnl LCXB01|ctg7180000005231

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000691093	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 5, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002658921	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Oct 17, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000691093

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 5, 2023)

germline

clinical testing

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

SCV002658921

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Oct 17, 2023)

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	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

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000691093.4

#	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 valine with glycine at codon 214 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 been identified in 1/251484 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

From Ambry Genetics, SCV002658921.2

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

Description

The p.V214G variant (also known as c.641T>G), located in coding exon 6 of the PMS2 gene, results from a T to G substitution at nucleotide position 641. The valine at codon 214 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious 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

Last Updated: Sep 29, 2024

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