NM_000535.7(PMS2):c.964G>A (p.Val322Ile) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: May 17, 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:: RCV000781751.2

Allele description [Variation Report for NM_000535.7(PMS2):c.964G>A (p.Val322Ile)]

NM_000535.7(PMS2):c.964G>A (p.Val322Ile)

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.964G>A (p.Val322Ile)

Other names:

p.V322I:GTT>ATT

HGVS:

NC_000007.14:g.5991997C>T
NG_008466.1:g.22110G>A
NM_000535.7:c.964G>AMANE SELECT
NM_001322003.2:c.559G>A
NM_001322004.2:c.559G>A
NM_001322005.2:c.559G>A
NM_001322006.2:c.964G>A
NM_001322007.2:c.646G>A
NM_001322008.2:c.646G>A
NM_001322009.2:c.559G>A
NM_001322010.2:c.559G>A
NM_001322011.2:c.31G>A
NM_001322012.2:c.31G>A
NM_001322013.2:c.391G>A
NM_001322014.2:c.964G>A
NM_001322015.2:c.655G>A
NP_000526.2:p.Val322Ile
NP_001308932.1:p.Val187Ile
NP_001308933.1:p.Val187Ile
NP_001308934.1:p.Val187Ile
NP_001308935.1:p.Val322Ile
NP_001308936.1:p.Val216Ile
NP_001308937.1:p.Val216Ile
NP_001308938.1:p.Val187Ile
NP_001308939.1:p.Val187Ile
NP_001308940.1:p.Val11Ile
NP_001308941.1:p.Val11Ile
NP_001308942.1:p.Val131Ile
NP_001308943.1:p.Val322Ile
NP_001308944.1:p.Val219Ile
LRG_161t1:c.964G>A
LRG_161:g.22110G>A
NC_000007.13:g.6031628C>T
NM_000535.5:c.964G>A
NM_000535.6:c.964G>A
NR_136154.1:n.1051G>A
p.V322I

Protein change:

V11I

Links:

dbSNP: rs587782208

NCBI 1000 Genomes Browser:

rs587782208

Molecular consequence:

NM_000535.7:c.964G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322003.2:c.559G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322004.2:c.559G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322005.2:c.559G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.964G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322007.2:c.646G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322008.2:c.646G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322009.2:c.559G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322010.2:c.559G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322011.2:c.31G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322012.2:c.31G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322013.2:c.391G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.964G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322015.2:c.655G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.1051G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000920041	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Sep 18, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26333163, 25186627 Citation Link,
SCV002047124	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (May 17, 2021)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25186627, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000920041

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Sep 18, 2017)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV002047124

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(May 17, 2021)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Classification of Amino Acid Substitutions in Mismatch Repair Proteins Using PON-MMR2.

Niroula A, Vihinen M.

Hum Mutat. 2015 Dec;36(12):1128-34. doi: 10.1002/humu.22900. Epub 2015 Sep 22.

PubMed [citation]

PMID:: 26333163

Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel.

Tung N, Battelli C, Allen B, Kaldate R, Bhatnagar S, Bowles K, Timms K, Garber JE, Herold C, Ellisen L, Krejdovsky J, DeLeonardis K, Sedgwick K, Soltis K, Roa B, Wenstrup RJ, Hartman AR.

Cancer. 2015 Jan 1;121(1):25-33. doi: 10.1002/cncr.29010. Epub 2014 Sep 3.

PubMed [citation]

PMID:: 25186627

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000920041.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: The PMS2 c.964G>A (p.Val322Ile) variant located in the Ribosomal protein S5 domain 2-type fold (via InterPro) involves the alteration of a conserved nucleotide and 2/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). However, these predictions have yet to be functionally assessed. This variant was found in 2/246084 control chromosomes at a frequency of 0.0000081, which does not exceed the estimated maximal expected allele frequency of a pathogenic PMS2 variant (0.0001136). However, the technology utilized for this dataset do not rule out pseudogene interference and thus this data needs to be cautiously considered. A publication, Tung_2015, reports the variant to have been found in one BrC pt, however, limited information is provided (ie, lack of cosegregation data). Multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.

#	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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV002047124.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

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

Last Updated: Sep 29, 2024

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