NM_000535.7(PMS2):c.2404C>T (p.Arg802Ter) AND PMS2-related disorder

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 4, 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:: RCV003415681.4

Allele description [Variation Report for NM_000535.7(PMS2):c.2404C>T (p.Arg802Ter)]

NM_000535.7(PMS2):c.2404C>T (p.Arg802Ter)

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.2404C>T (p.Arg802Ter)

HGVS:

NC_000007.14:g.5977629G>A
NG_008466.1:g.36478C>T
NM_000535.7:c.2404C>TMANE SELECT
NM_001322003.2:c.1999C>T
NM_001322004.2:c.1999C>T
NM_001322005.2:c.1999C>T
NM_001322006.2:c.2248C>T
NM_001322007.2:c.2086C>T
NM_001322008.2:c.2086C>T
NM_001322009.2:c.2032C>T
NM_001322010.2:c.1843C>T
NM_001322011.2:c.1471C>T
NM_001322012.2:c.1471C>T
NM_001322013.2:c.1831C>T
NM_001322014.2:c.2437C>T
NM_001322015.2:c.2095C>T
NP_000526.2:p.Arg802Ter
NP_001308932.1:p.Arg667Ter
NP_001308933.1:p.Arg667Ter
NP_001308934.1:p.Arg667Ter
NP_001308935.1:p.Arg750Ter
NP_001308936.1:p.Arg696Ter
NP_001308937.1:p.Arg696Ter
NP_001308938.1:p.Arg678Ter
NP_001308939.1:p.Arg615Ter
NP_001308940.1:p.Arg491Ter
NP_001308941.1:p.Arg491Ter
NP_001308942.1:p.Arg611Ter
NP_001308943.1:p.Arg813Ter
NP_001308944.1:p.Arg699Ter
LRG_161t1:c.2404C>T
LRG_161:g.36478C>T
NC_000007.13:g.6017260G>A
NM_000535.5:c.2404C>T
NM_000535.6:c.2404C>T
NR_136154.1:n.2448C>T
p.R802*

Protein change:

R491*; ARG802TER

Links:

OMIM: 600259.0004; dbSNP: rs63751466

NCBI 1000 Genomes Browser:

rs63751466

Molecular consequence:

NR_136154.1:n.2448C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000535.7:c.2404C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322003.2:c.1999C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322004.2:c.1999C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322005.2:c.1999C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322006.2:c.2248C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322007.2:c.2086C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322008.2:c.2086C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322009.2:c.2032C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322010.2:c.1843C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322011.2:c.1471C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322012.2:c.1471C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322013.2:c.1831C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322014.2:c.2437C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322015.2:c.2095C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: PMS2-related disorder
Synonyms:: PMS2-related condition
Identifiers:

Recent activity

Clear Turn Off Turn On

Homo sapiens serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitr...
Homo sapiens serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 3, mRNA (cDNA clone IMAGE:3925035), partial cds
gi|15341984|gb|BC013189.1|

Nucleotide
Homologene neighbors for GEO Profiles (Select 113041074) (0)
GEO Profiles
Chromosome neighbors for GEO Profiles (Select 113037228) (20)
GEO Profiles
DC030491 Osada Taira anterior endomesoderm (AEM) pCS105 cDNA library Xenopus lae...
DC030491 Osada Taira anterior endomesoderm (AEM) pCS105 cDNA library Xenopus laevis cDNA clone rxlk159l23ex 3', mRNA sequence
gi|118979626|gnl|dbEST|43280149|dbj 0491.1|

Nucleotide
GPR35 G protein-coupled receptor 35 [Canis lupus familiaris]
GPR35 G protein-coupled receptor 35 [Canis lupus familiaris]
Gene ID:100855802

Gene

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
SCV004113956	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 4, 2023)	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

SCV004113956

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 4, 2023)

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	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 PreventionGenetics, part of Exact Sciences, SCV004113956.1

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

Description

The PMS2 c.2404C>T variant is predicted to result in premature protein termination (p.Arg802*). This variant has been reported in individuals with Lynch syndrome (Table 1, Senter et al. 2008. PubMed ID: 18602922; Table S2, ten Broeke et al. 2015. PubMed ID: 25512458; Table S2, Rosty. 2016. PubMed ID: 26895986; Table 1, Okkels et al. 2019. PubMed ID: 31433215; Table 2, Manchana and Triratanachat. 2021. PubMed ID: 34048176). It has been reported in a case of pediatric embryonal rhabdomyosarcoma (Table 3, referred to as 7:6017260G>A, Li et al. 2020. PubMed ID: 33372952). It has also been reported in the homozygous state and presumed compound heterozygous state in individuals with constitutional mismatch repair deficiency syndrome (De Vos et al. 2004. PubMed ID: 15077197; De Vos et al. 2006. PubMed ID: 16507833; Perez-Valencia et al. 2020. PubMed ID: 32773772; Gupta et al. 2020. PubMed ID: 32876971). This variant is reported in 6 of ~256,000 alleles in gnomAD and is interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/9237/). However, this region has high homology with the pseudogene PMS2CL, and data should be interpreted with caution (http://gnomad.broadinstitute.org/variant/7-6017260-G-A). Nonsense variants in PMS2 are known to be causative. This variant is interpreted as 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: Oct 8, 2024

ClinVar

Relating variation to medicine