NM_000535.7(PMS2):c.2155C>T (p.Gln719Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 2, 2024
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:: RCV000482925.9

Allele description [Variation Report for NM_000535.7(PMS2):c.2155C>T (p.Gln719Ter)]

NM_000535.7(PMS2):c.2155C>T (p.Gln719Ter)

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.2155C>T (p.Gln719Ter)

HGVS:

NC_000007.14:g.5982843G>A
NG_008466.1:g.31264C>T
NM_000535.7:c.2155C>TMANE SELECT
NM_001322003.2:c.1750C>T
NM_001322004.2:c.1750C>T
NM_001322005.2:c.1750C>T
NM_001322006.2:c.1999C>T
NM_001322007.2:c.1837C>T
NM_001322008.2:c.1837C>T
NM_001322009.2:c.1750C>T
NM_001322010.2:c.1594C>T
NM_001322011.2:c.1222C>T
NM_001322012.2:c.1222C>T
NM_001322013.2:c.1582C>T
NM_001322014.2:c.2155C>T
NM_001322015.2:c.1846C>T
NP_000526.2:p.Gln719Ter
NP_001308932.1:p.Gln584Ter
NP_001308933.1:p.Gln584Ter
NP_001308934.1:p.Gln584Ter
NP_001308935.1:p.Gln667Ter
NP_001308936.1:p.Gln613Ter
NP_001308937.1:p.Gln613Ter
NP_001308938.1:p.Gln584Ter
NP_001308939.1:p.Gln532Ter
NP_001308940.1:p.Gln408Ter
NP_001308941.1:p.Gln408Ter
NP_001308942.1:p.Gln528Ter
NP_001308943.1:p.Gln719Ter
NP_001308944.1:p.Gln616Ter
LRG_161t1:c.2155C>T
LRG_161:g.31264C>T
NC_000007.13:g.6022474G>A
NM_000535.5:c.2155C>T
NM_000535.6:c.2155C>T
NR_136154.1:n.2242C>T
p.Gln719*

Protein change:

Q408*

Links:

dbSNP: rs876659480

NCBI 1000 Genomes Browser:

rs876659480

Molecular consequence:

NR_136154.1:n.2242C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000535.7:c.2155C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322003.2:c.1750C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322004.2:c.1750C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322005.2:c.1750C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322006.2:c.1999C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322007.2:c.1837C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322008.2:c.1837C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322009.2:c.1750C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322010.2:c.1594C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322011.2:c.1222C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322012.2:c.1222C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322013.2:c.1582C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322014.2:c.2155C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322015.2:c.1846C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000569464	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jan 2, 2024)	germline	clinical testing	Citation Link,
SCV000884399	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Pathogenic (Jun 23, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000569464

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jan 2, 2024)

germline

clinical testing

Citation Link,

SCV000884399

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Pathogenic
(Jun 23, 2017)

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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000569464.5

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

Description

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; This variant is associated with the following publications: (PMID: 25111426, 32782288, 25512458, 26110232, 31948886, 27435373, 24362816, 21376568, 35734982)

#	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 ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000884399.1

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

Description

The PMS2 c.2155C>T;p.Gln719Ter variant has been described in at least one family with a clinical diagnosis of Lynch syndrome (ten Broeke 2015). The variant is listed in the ClinVar database (Variation ID: 231993), but is not listed in the dbSNP variant database. The variant is listed in the Genome Aggregation Database with an allele frequency of 0.0008622 percent (2/231974 alleles). This variant introduces a premature termination codon and is predicted to result in a truncated or absent protein. Considering available information, this variant is classified as pathogenic. References: ten Broeke SW et al. Lynch syndrome caused by germline PMS2 mutations: delineating the cancer risk. J Clin Oncol. 2015 Feb 1;33(4):319-25.

#	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

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