NM_000535.7(PMS2):c.125TAG[1] (p.Val43del) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 9, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000568948.3

Allele description [Variation Report for NM_000535.7(PMS2):c.125TAG[1] (p.Val43del)]

NM_000535.7(PMS2):c.125TAG[1] (p.Val43del)

Gene:

PMS2:PMS1 homolog 2, mismatch repair system component [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

7p22.1

Genomic location:

Preferred name:

NM_000535.7(PMS2):c.125TAG[1] (p.Val43del)

HGVS:

NC_000007.14:g.6005925CTA[1]
NG_008466.1:g.8177TAG[1]
NG_050738.1:g.1675CTA[1]
NM_000535.7:c.125TAG[1]MANE SELECT
NM_001322003.2:c.-281TAG[1]
NM_001322004.2:c.-242-1869_-242-1867del
NM_001322005.2:c.-281TAG[1]
NM_001322006.2:c.125TAG[1]
NM_001322007.2:c.-91TAG[1]
NM_001322008.2:c.-52-1869_-52-1867del
NM_001322009.2:c.-281TAG[1]
NM_001322010.2:c.-242-1869_-242-1867del
NM_001322011.2:c.-760TAG[1]
NM_001322012.2:c.-760TAG[1]
NM_001322013.2:c.-281TAG[1]
NM_001322014.2:c.125TAG[1]
NM_001322015.2:c.-360TAG[1]
NP_000526.2:p.Val43del
NP_001308935.1:p.Val43del
NP_001308943.1:p.Val43del
LRG_161t1:c.128_130del
LRG_161:g.8177TAG[1]
NC_000007.13:g.6045556CTA[1]
NC_000007.13:g.6045556_6045558del
NM_000535.5:c.128_130delTAG
NM_000535.6:c.128_130del
NR_136154.1:n.212TAG[1]

Protein change:

V43del

Links:

dbSNP: rs1064794820

NCBI 1000 Genomes Browser:

rs1064794820

Molecular consequence:

NM_001322003.2:c.-281TAG[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322005.2:c.-281TAG[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322007.2:c.-91TAG[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322009.2:c.-281TAG[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322011.2:c.-760TAG[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322012.2:c.-760TAG[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322013.2:c.-281TAG[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322015.2:c.-360TAG[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000535.7:c.125TAG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001322006.2:c.125TAG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001322014.2:c.125TAG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001322004.2:c.-242-1869_-242-1867del - intron variant - [Sequence Ontology: SO:0001627]
NM_001322008.2:c.-52-1869_-52-1867del - intron variant - [Sequence Ontology: SO:0001627]
NM_001322010.2:c.-242-1869_-242-1867del - intron variant - [Sequence Ontology: SO:0001627]
NR_136154.1:n.212TAG[1] - 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
SCV000663470	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Jun 9, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000663470

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Jun 9, 2021)

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

Details of each submission

From Ambry Genetics, SCV000663470.5

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

Description

The c.128_130delTAG variant (also known as p.V43del) is located in coding exon 2 of the PMS2 gene. This variant results from an in-frame TAG deletion at nucleotide positions 128 to 130. This results in the in-frame deletion of a valine at codon 43. This variant has been confirmed in trans with a PMS2 likely pathogenic variant in a proband with clinical features of constitutional mismatch repair deficiency (CMMRD) syndrome (Ambry internal data). Based on internal structural analysis, p.V43del is deleterious and is less tolerated compared to nearby pathogenic variants (Ambry internal data). The deleted amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#	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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