NM_000535.7(PMS2):c.142G>A (p.Asp48Asn) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 17, 2023
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:: RCV000220384.4

Allele description [Variation Report for NM_000535.7(PMS2):c.142G>A (p.Asp48Asn)]

NM_000535.7(PMS2):c.142G>A (p.Asp48Asn)

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.142G>A (p.Asp48Asn)

Other names:

p.Asp48Asn

HGVS:

NC_000007.14:g.6005913C>T
NG_008466.1:g.8194G>A
NG_050738.1:g.1663C>T
NM_000535.7:c.142G>AMANE SELECT
NM_001322003.2:c.-264G>A
NM_001322004.2:c.-242-1855G>A
NM_001322005.2:c.-264G>A
NM_001322006.2:c.142G>A
NM_001322007.2:c.-74G>A
NM_001322008.2:c.-52-1855G>A
NM_001322009.2:c.-264G>A
NM_001322010.2:c.-242-1855G>A
NM_001322011.2:c.-743G>A
NM_001322012.2:c.-743G>A
NM_001322013.2:c.-264G>A
NM_001322014.2:c.142G>A
NM_001322015.2:c.-343G>A
NP_000526.2:p.Asp48Asn
NP_001308935.1:p.Asp48Asn
NP_001308943.1:p.Asp48Asn
LRG_161t1:c.142G>A
LRG_161:g.8194G>A
NC_000007.13:g.6045544C>T
NM_000535.5:c.142G>A
NM_000535.6:c.142G>A
NR_136154.1:n.229G>A

Protein change:

D48N

Links:

dbSNP: rs755665894

NCBI 1000 Genomes Browser:

rs755665894

Molecular consequence:

NM_001322003.2:c.-264G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322005.2:c.-264G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322007.2:c.-74G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322009.2:c.-264G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322011.2:c.-743G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322012.2:c.-743G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322013.2:c.-264G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322015.2:c.-343G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322004.2:c.-242-1855G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001322008.2:c.-52-1855G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001322010.2:c.-242-1855G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000535.7:c.142G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.142G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.142G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.229G>A - 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
SCV000277905	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Nov 17, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000277905

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Nov 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

Details of each submission

From Ambry Genetics, SCV000277905.7

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

Description

The p.D48N variant (also known as c.142G>A), located in coding exon 2 of the PMS2 gene, results from a G to A substitution at nucleotide position 142. The aspartic acid at codon 48 is replaced by asparagine, an amino acid with highly similar properties. This alteration is detected in at least one individual whose Lynch-related tumor demonstrated microsatellite stability and/or normal mismatch repair protein expression on immunohistochemistry (Ambry internal data). This alteration was also seen to co-segregate in a family that meets Amsterdam criteria (Ambry internal data). 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 conflicting 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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