NM_000535.7(PMS2):c.2062A>G (p.Ile688Val) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 18, 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:: RCV000562935.6

Allele description [Variation Report for NM_000535.7(PMS2):c.2062A>G (p.Ile688Val)]

NM_000535.7(PMS2):c.2062A>G (p.Ile688Val)

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.2062A>G (p.Ile688Val)

HGVS:

NC_000007.14:g.5982936T>C
NG_008466.1:g.31171A>G
NM_000535.7:c.2062A>GMANE SELECT
NM_001322003.2:c.1657A>G
NM_001322004.2:c.1657A>G
NM_001322005.2:c.1657A>G
NM_001322006.2:c.1906A>G
NM_001322007.2:c.1744A>G
NM_001322008.2:c.1744A>G
NM_001322009.2:c.1657A>G
NM_001322010.2:c.1501A>G
NM_001322011.2:c.1129A>G
NM_001322012.2:c.1129A>G
NM_001322013.2:c.1489A>G
NM_001322014.2:c.2062A>G
NM_001322015.2:c.1753A>G
NP_000526.2:p.Ile688Val
NP_001308932.1:p.Ile553Val
NP_001308933.1:p.Ile553Val
NP_001308934.1:p.Ile553Val
NP_001308935.1:p.Ile636Val
NP_001308936.1:p.Ile582Val
NP_001308937.1:p.Ile582Val
NP_001308938.1:p.Ile553Val
NP_001308939.1:p.Ile501Val
NP_001308940.1:p.Ile377Val
NP_001308941.1:p.Ile377Val
NP_001308942.1:p.Ile497Val
NP_001308943.1:p.Ile688Val
NP_001308944.1:p.Ile585Val
LRG_161t1:c.2062A>G
LRG_161:g.31171A>G
NC_000007.13:g.6022567T>C
NM_000535.5:c.2062A>G
NM_000535.6:c.2062A>G
NR_136154.1:n.2149A>G

Protein change:

I377V

Links:

dbSNP: rs1060503144

NCBI 1000 Genomes Browser:

rs1060503144

Molecular consequence:

NM_000535.7:c.2062A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322003.2:c.1657A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322004.2:c.1657A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322005.2:c.1657A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.1906A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322007.2:c.1744A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322008.2:c.1744A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322009.2:c.1657A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322010.2:c.1501A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322011.2:c.1129A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322012.2:c.1129A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322013.2:c.1489A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.2062A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322015.2:c.1753A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.2149A>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000670771	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Sep 17, 2020)	germline	clinical testing	Citation Link,
SCV002530255	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Mar 18, 2022)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000670771

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Sep 17, 2020)

germline

clinical testing

Citation Link,

SCV002530255

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Mar 18, 2022)

germline

curation

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, curation

Details of each submission

From Ambry Genetics, SCV000670771.5

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

Description

The p.I688V variant (also known as c.2062A>G), located in coding exon 12 of the PMS2 gene, results from an A to G substitution at nucleotide position 2062. The isoleucine at codon 688 is replaced by valine, an amino acid with highly similar properties. This missense alteration is located in a region that has a low rate of benign missense variation (Lek M et al. Nature. 2016 Aug 18;536(7616):285-91; DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources. Firth H.V. et al. 2009. Am.J.Hum.Genet. 84, 524-533 (DOI: dx.doi.org/10/1016/j.ajhg.2009.03.010)). 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 Sema4, Sema4, SCV002530255.1

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

#	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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