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NM_000059.4(BRCA2):c.2T>C (p.Met1Thr) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 5, 2022
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:
RCV000165930.10

Allele description [Variation Report for NM_000059.4(BRCA2):c.2T>C (p.Met1Thr)]

NM_000059.4(BRCA2):c.2T>C (p.Met1Thr)

Gene:
BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q13.1
Genomic location:
Preferred name:
NM_000059.4(BRCA2):c.2T>C (p.Met1Thr)
HGVS:
  • NC_000013.11:g.32316462T>C
  • NG_012772.3:g.5983T>C
  • NG_017006.2:g.3902A>G
  • NM_000059.4:c.2T>CMANE SELECT
  • NP_000050.2:p.Met1Thr
  • NP_000050.3:p.Met1Thr
  • LRG_293t1:c.2T>C
  • LRG_293:g.5983T>C
  • LRG_293p1:p.Met1Thr
  • NC_000013.10:g.32890599T>C
  • NG_017006.1:g.493A>G
  • NM_000059.3:c.2T>C
  • p.M1?
Protein change:
M1T
Links:
dbSNP: rs80358547
NCBI 1000 Genomes Browser:
rs80358547
Molecular consequence:
  • NM_000059.4:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_000059.4:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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
SCV000216686Ambry Genetics
criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)		Pathogenic
(Apr 5, 2022) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Mutations predisposing to breast cancer in 12 candidate genes in breast cancer patients from Poland.

Cybulski C, Lubiński J, Wokołorczyk D, Kuźniak W, Kashyap A, Sopik V, Huzarski T, Gronwald J, Byrski T, Szwiec M, Jakubowska A, Górski B, Dębniak T, Narod SA, Akbari MR.

Clin Genet. 2015 Oct;88(4):366-70. doi: 10.1111/cge.12524. Epub 2014 Nov 13.

PubMed [citation]
PMID:
25330149

Details of each submission

From Ambry Genetics, SCV000216686.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The p.M1? pathogenic mutation (also known as c.2T>C) is located in coding exon 1 of the BRCA2 gene and results from a T to C substitution at nucleotide position 2. This alters the methionine residue at the initiation codon (ATG). This mutation was observed in a Polish individual diagnosed with ovarian cancer at age 60 (Jakubowska A et al. Eur. J. Hum. Genet. 2003 Dec;11(12):955-8). In addition, this mutation and other mutations that affect the initiation codon have been observed in multiple other breast and/or ovarian cancer families to date (Lubinski J et al. Fam. Cancer. 2004;3(1):1-10; Thomassen M et al. Breast Cancer Res. Treat. 2012 Apr;132(3):1009-23; Santos C et al. J. Mol. Diagn. 2014 May;16(3):324-34; Cybulski C et al. Clin. Genet. 2015 Oct;88(4):366-70). Of note, this alteration is also designated as 230T>C in published literature. In addition to the clinical data presented in the literature, sequence variations that modify the initiation codon are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Apr 20, 2024