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NM_000535.7(PMS2):c.250A>C (p.Thr84Pro) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Aug 15, 2023
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:
RCV000563874.7

Allele description [Variation Report for NM_000535.7(PMS2):c.250A>C (p.Thr84Pro)]

NM_000535.7(PMS2):c.250A>C (p.Thr84Pro)

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.250A>C (p.Thr84Pro)
HGVS:
  • NC_000007.14:g.6003972T>G
  • NG_008466.1:g.10135A>C
  • NM_000535.7:c.250A>CMANE SELECT
  • NM_001322003.2:c.-156A>C
  • NM_001322004.2:c.-156A>C
  • NM_001322005.2:c.-156A>C
  • NM_001322006.2:c.250A>C
  • NM_001322007.2:c.35A>C
  • NM_001322008.2:c.35A>C
  • NM_001322009.2:c.-156A>C
  • NM_001322010.2:c.-156A>C
  • NM_001322011.2:c.-635A>C
  • NM_001322012.2:c.-635A>C
  • NM_001322013.2:c.-156A>C
  • NM_001322014.2:c.250A>C
  • NM_001322015.2:c.-235A>C
  • NP_000526.2:p.Thr84Pro
  • NP_001308935.1:p.Thr84Pro
  • NP_001308936.1:p.Asn12Thr
  • NP_001308937.1:p.Asn12Thr
  • NP_001308943.1:p.Thr84Pro
  • LRG_161t1:c.250A>C
  • LRG_161:g.10135A>C
  • NC_000007.13:g.6043603T>G
  • NM_000535.5:c.250A>C
  • NR_136154.1:n.337A>C
Protein change:
N12T
Links:
dbSNP: rs1554304938
NCBI 1000 Genomes Browser:
rs1554304938
Molecular consequence:
  • NM_001322003.2:c.-156A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322004.2:c.-156A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322005.2:c.-156A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322009.2:c.-156A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322010.2:c.-156A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322011.2:c.-635A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322012.2:c.-635A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322013.2:c.-156A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322015.2:c.-235A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000535.7:c.250A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322006.2:c.250A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322007.2:c.35A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322008.2:c.35A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322014.2:c.250A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_136154.1:n.337A>C - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000664963Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Aug 15, 2023) 		germlineclinical testing

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

Citation Link,

SCV002530312Sema4, Sema4
criteria provided, single submitter

(Sema4 Curation Guidelines)		Uncertain significance
(Feb 26, 2022) 		germlinecuration

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing, curation

Citations

PubMed

Identification of a novel pathogenic variant in PALB2 and BARD1 genes by a multigene sequencing panel in triple negative breast cancer in Morocco.

Laraqui A, Cavaillé M, Uhrhammer N, ElBiad O, Bidet Y, El Rhaffouli H, El Anaz H, Rahali DM, Kouach J, Guelzim K, Badaoui B, AlBouzidi A, Oukabli M, Tanz R, Sbitti Y, Ichou M, Ennibi K, Sekhsokh Y, Bignon YJ.

J Genomics. 2021;9:43-54. doi: 10.7150/jgen.61713.

PubMed [citation]
PMID:
34646395
PMCID:
PMC8490085

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Breast Cancer Association Consortium., Dorling L, Carvalho S, Allen J, González-Neira A, Luccarini C, Wahlström C, Pooley KA, Parsons MT, Fortuno C, Wang Q, Bolla MK, Dennis J, Keeman R, Alonso MR, Álvarez N, Herraez B, Fernandez V, Núñez-Torres R, Osorio A, Valcich J, Li M, et al.

N Engl J Med. 2021 Feb 4;384(5):428-439. doi: 10.1056/NEJMoa1913948. Epub 2021 Jan 20.

PubMed [citation]
PMID:
33471991
PMCID:
PMC7611105

Details of each submission

From Ambry Genetics, SCV000664963.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The p.T84P variant (also known as c.250A>C), located in coding exon 3 of the PMS2 gene, results from an A to C substitution at nucleotide position 250. The amino acid change results in threonine to proline at codon 84, an amino acid with highly similar properties. This nucleotide position and amino acid position are not well conserved in available vertebrate species. This change occurs in the last base pair of coding exon 3, which makes it likely to have some effect on normal mRNA splicing; however, RNA studies have demonstrated that this alteration does not result in abnormal splicing in the set of samples tested (Ambry internal data). This variant was reported in a cohort of Moroccan triple negative breast cancer patients (Laraqui A et al. J Genomics, 2021 Sep;9:43-54). In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Sema4, Sema4, SCV002530312.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024