NM_000059.4(BRCA2):c.2T>A (p.Met1Lys) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 17, 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:: RCV000496424.10

Allele description [Variation Report for NM_000059.4(BRCA2):c.2T>A (p.Met1Lys)]

NM_000059.4(BRCA2):c.2T>A (p.Met1Lys)

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>A (p.Met1Lys)

HGVS:

NC_000013.11:g.32316462T>A
NG_012772.3:g.5983T>A
NG_017006.2:g.3902A>T
NM_000059.4:c.2T>AMANE SELECT
NP_000050.2:p.Met1Lys
NP_000050.3:p.Met1Lys
LRG_293t1:c.2T>A
LRG_293:g.5983T>A
LRG_293p1:p.Met1Lys
NC_000013.10:g.32890599T>A
NG_017006.1:g.493A>T
NM_000059.3:c.2T>A

Protein change:

M1K

Links:

dbSNP: rs80358547

NCBI 1000 Genomes Browser:

rs80358547

Molecular consequence:

NM_000059.4:c.2T>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_000059.4:c.2T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary breast ovarian cancer syndrome
Synonyms:: Hereditary breast and ovarian cancer syndrome; Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000587524	Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto - The Canadian Open Genetics Repository (COGR)	no assertion criteria provided	Pathogenic (Jan 31, 2014)	germline	research
SCV003442054	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 17, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 14647210, 18182601, 21769658, 24156927, 24607278, 25330149, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000587524

Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto - The Canadian Open Genetics Repository (COGR)

no assertion criteria provided

Pathogenic
(Jan 31, 2014)

germline

research

SCV003442054

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 17, 2022)

germline

clinical testing

PubMed (7)
[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	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A high frequency of BRCA2 gene mutations in Polish families with ovarian and stomach cancer.

Jakubowska A, Scott R, Menkiszak J, Gronwald J, Byrski T, Huzarski T, Górski B, Cybulski C, Debniak T, Kowalska E, Starzyńska T, Ławniczak M, Narod S, Lubinski J.

Eur J Hum Genet. 2003 Dec;11(12):955-8.

PubMed [citation]

PMID:: 14647210

Variation of breast cancer risk among BRCA1/2 carriers.

Begg CB, Haile RW, Borg A, Malone KE, Concannon P, Thomas DC, Langholz B, Bernstein L, Olsen JH, Lynch CF, Anton-Culver H, Capanu M, Liang X, Hummer AJ, Sima C, Bernstein JL.

JAMA. 2008 Jan 9;299(2):194-201. doi: 10.1001/jama.2007.55-a.

PubMed [citation]

PMID:: 18182601
PMCID:: PMC2714486

See all PubMed Citations (7)

Details of each submission

From Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto - The Canadian Open Genetics Repository (COGR), SCV000587524.2

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

#	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 Invitae, SCV003442054.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. This sequence change affects the initiator methionine of the BRCA2 mRNA. The next in-frame methionine is located at codon 124. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individual(s) with breast cancer and/or personal or family history of breast and/or ovarian cancer (PMID: 14647210, 18182601, 21769658, 24156927, 24607278, 25330149; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 431282).

#	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: May 1, 2024

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