NM_000535.7(PMS2):c.247_250dup (p.Thr84fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 30, 2021
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:: RCV000479446.5

Allele description [Variation Report for NM_000535.7(PMS2):c.247_250dup (p.Thr84fs)]

NM_000535.7(PMS2):c.247_250dup (p.Thr84fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

7p22.1

Genomic location:

Preferred name:

NM_000535.7(PMS2):c.247_250dup (p.Thr84fs)

HGVS:

NC_000007.14:g.6003972_6003975dup
NG_008466.1:g.10132_10135dup
NM_000535.7:c.247_250dupMANE SELECT
NM_001322003.2:c.-159_-156dup
NM_001322004.2:c.-159_-156dup
NM_001322005.2:c.-159_-156dup
NM_001322006.2:c.247_250dup
NM_001322007.2:c.32_35dup
NM_001322008.2:c.32_35dup
NM_001322009.2:c.-159_-156dup
NM_001322010.2:c.-159_-156dup
NM_001322011.2:c.-638_-635dup
NM_001322012.2:c.-638_-635dup
NM_001322013.2:c.-159_-156dup
NM_001322014.2:c.247_250dup
NM_001322015.2:c.-238_-235dup
NP_000526.2:p.Thr84fs
NP_001308935.1:p.Thr84fs
NP_001308936.1:p.Asn12_Asp13insTer
NP_001308937.1:p.Asn12_Asp13insTer
NP_001308943.1:p.Thr84fs
LRG_161t1:c.247_250dup
LRG_161:g.10132_10135dup
NC_000007.13:g.6043602_6043603insTTAA
NC_000007.13:g.6043603_6043606dup
NM_000535.5:c.247_250dupTTAA
NR_136154.1:n.334_337dup

Protein change:

T84fs

Links:

dbSNP: rs1554304940

NCBI 1000 Genomes Browser:

rs1554304940

Molecular consequence:

NM_001322003.2:c.-159_-156dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322004.2:c.-159_-156dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322005.2:c.-159_-156dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322009.2:c.-159_-156dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322010.2:c.-159_-156dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322011.2:c.-638_-635dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322012.2:c.-638_-635dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322013.2:c.-159_-156dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322015.2:c.-238_-235dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000535.7:c.247_250dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322006.2:c.247_250dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322014.2:c.247_250dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322007.2:c.32_35dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001322008.2:c.32_35dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NR_136154.1:n.334_337dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001322007.2:c.32_35dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001322008.2:c.32_35dup - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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
SCV000569466	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jun 6, 2016)	germline	clinical testing	Citation Link,
SCV002019441	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 30, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000569466

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Jun 6, 2016)

germline

clinical testing

Citation Link,

SCV002019441

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 30, 2021)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
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 GeneDx, SCV000569466.3

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

Description

This duplication of 4 nucleotides in PMS2 is denoted c.247_250dupTTAA at the cDNA level and p.Thr84IlefsX9 (T84IfsX9) at the protein level. The normal sequence, with the bases that are duplicated in braces, is AGGC[TTAA]GTAA. The duplication causes a frameshift which changes a Threonine to an Isoleucine at codon 84, and creates a premature stop codon at position 9 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. PMS2 c.247_250dupTTAA has been identified in individuals with Lynch syndrome-associated cancers, with tumor testing in at least one of these individuals showing microsatellite instability (MSI-H) and loss of PMS2 protein expression (Dudley 2015, Suerink 2015). We consider this variant to be pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV002019441.3

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

#	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

ClinVar

Relating variation to medicine