NM_000059.4(BRCA2):c.3554_3555del (p.Thr1185fs) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 25, 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:: RCV000496524.16

Allele description [Variation Report for NM_000059.4(BRCA2):c.3554_3555del (p.Thr1185fs)]

NM_000059.4(BRCA2):c.3554_3555del (p.Thr1185fs)

Gene:

BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.3554_3555del (p.Thr1185fs)

Other names:

3782delCA

HGVS:

NC_000013.10:g.32912045_32912046del
NC_000013.11:g.32337909_32337910del
NG_012772.3:g.27430_27431del
NM_000059.4:c.3554_3555delMANE SELECT
NP_000050.3:p.Thr1185fs
LRG_293:g.27430_27431del
NC_000013.10:g.32912045_32912046del
NC_000013.10:g.32912046_32912047del
NC_000013.10:g.32912046_32912047delCA
NM_000059.3:c.3554_3555delCA
NM_000059.4:c.3554_3555del
U43746.1:n.3782_3783delCA

Links:

Breast Cancer Information Core (BIC) (BRCA2): 3782&base_change=del CA; dbSNP: rs80359389

NCBI 1000 Genomes Browser:

rs80359389

Molecular consequence:

NM_000059.4:c.3554_3555del - frameshift variant - [Sequence Ontology: SO:0001589]

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

Recent activity

Clear Turn Off Turn On

PREDICTED: Triticum aestivum glutamine synthetase-like (LOC123128319), mRNA
PREDICTED: Triticum aestivum glutamine synthetase-like (LOC123128319), mRNA
gi|2123888177|ref|XM_044548287.1|

Nucleotide
CBXT7878.g1 NICHD_XGC_trop_25 Xenopus tropicalis cDNA clone IMAGE:8889916 3', mR...
CBXT7878.g1 NICHD_XGC_trop_25 Xenopus tropicalis cDNA clone IMAGE:8889916 3', mRNA sequence
gi|133814576|gnl|dbEST|45244183|gb| 223.1|

Nucleotide
BioSample Links for SRA (Select 15743097) (1)
BioSample
Model organism or animal sample from Megalobrama hoffmanni
Model organism or animal sample from Megalobrama hoffmanni

biosample
Protein Links for Gene (Select 75284) (5)
Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000587673	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
SCV001583196	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 25, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20104584, 15131399, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000587673

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

SCV001583196

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 25, 2022)

germline

clinical testing

PubMed (3)
[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

Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.

Borg A, Haile RW, Malone KE, Capanu M, Diep A, Törngren T, Teraoka S, Begg CB, Thomas DC, Concannon P, Mellemkjaer L, Bernstein L, Tellhed L, Xue S, Olson ER, Liang X, Dolle J, Børresen-Dale AL, Bernstein JL.

Hum Mutat. 2010 Mar;31(3):E1200-40. doi: 10.1002/humu.21202.

PubMed [citation]

PMID:: 20104584
PMCID:: PMC2928257

Cancer variation associated with the position of the mutation in the BRCA2 gene.

Lubinski J, Phelan CM, Ghadirian P, Lynch HT, Garber J, Weber B, Tung N, Horsman D, Isaacs C, Monteiro AN, Sun P, Narod SA.

Fam Cancer. 2004;3(1):1-10.

PubMed [citation]

PMID:: 15131399

See all PubMed Citations (3)

Details of each submission

From Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto - The Canadian Open Genetics Repository (COGR), SCV000587673.1

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001583196.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr1185Serfs*2) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This premature translational stop signal has been observed in individual(s) with ovarian and/or other cancer (PMID: 15131399). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 51485).

#	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 26, 2024

ClinVar

Relating variation to medicine