NM_000059.4(BRCA2):c.5681dup (p.Tyr1894Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 8, 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:: RCV000129296.20

Allele description [Variation Report for NM_000059.4(BRCA2):c.5681dup (p.Tyr1894Ter)]

NM_000059.4(BRCA2):c.5681dup (p.Tyr1894Ter)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.5681dup (p.Tyr1894Ter)

Other names:

p.Tyr1894X

HGVS:

NC_000013.11:g.32340036dup
NG_012772.3:g.29557dup
NM_000059.4:c.5681dupMANE SELECT
NP_000050.3:p.Tyr1894Ter
LRG_293:g.29557dup
NC_000013.10:g.32914172_32914173insA
NC_000013.10:g.32914173dup
NM_000059.3:c.5681dupA
NM_000059.4:c.5681dup
U43746.1:n.5909_5910insA
p.Tyr1894*
p.Y1894*

Nucleotide change:

5909insA

Protein change:

Y1894*

Links:

Breast Cancer Information Core (BIC) (BRCA2): 5909&base_change=ins A; dbSNP: rs80359527

NCBI 1000 Genomes Browser:

rs80359527

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

Recent activity

Clear Turn Off Turn On

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
SCV000184057	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Apr 5, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16683254, 27721756 Citation Link,
SCV000911073	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 8, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 16683254, 17851763, 27153395, 28294317, 28724667, 28993434, 29907814, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000184057

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Apr 5, 2022)

germline

clinical testing

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

Citation Link,

SCV000911073

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 8, 2023)

germline

clinical testing

PubMed (8)
[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

Citations

PubMed

Synchronous Onset of Breast and Pancreatic Cancers: Results of Germline and Somatic Genetic Analysis.

Castro M, Vierkoetter K, Prager D, Montgomery S, Sedgwick K.

Case Rep Oncol. 2016 May-Aug;9(2):387-394.

PubMed [citation]

PMID:: 27721756
PMCID:: PMC5043351

A DGGE system for comprehensive mutation screening of BRCA1 and BRCA2: application in a Dutch cancer clinic setting.

van der Hout AH, van den Ouweland AM, van der Luijt RB, Gille HJ, Bodmer D, Brüggenwirth H, Mulder IM, van der Vlies P, Elfferich P, Huisman MT, ten Berge AM, Kromosoeto J, Jansen RP, van Zon PH, Vriesman T, Arts N, Lange MB, Oosterwijk JC, Meijers-Heijboer H, Ausems MG, Hoogerbrugge N, Verhoef S, et al.

Hum Mutat. 2006 Jul;27(7):654-66.

PubMed [citation]

PMID:: 16683254

See all PubMed Citations (9)

Details of each submission

From Ambry Genetics, SCV000184057.8

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

Description

The c.5681dupA pathogenic mutation (also known as p.Y1894*), located in coding exon 10 of the BRCA2 gene, results from a duplication of A at position 5681. This changes the amino acid from a tyrosine to a stop codon within coding exon 10. This pathogenic mutation has been previously reported in Asian, European, and South American breast/ovarian cohorts (van der Hout AH et al. Hum. Mutat. 2006 Jul;27(7):654-66; Li WF et al. Breast Cancer Res. Treat. 2008 Jul;110(1):99-109; Solano AR et al. Springerplus. 2012 Sep;1:20; Castro M et al. Case Rep. Oncol. 2016 Jul;9(2):387-394; Sun J et al. Clin. Cancer Res. 2017 Oct;23(20):6113-6119; Wen WX et al. J. Med. Genet. 2018 Feb;55(2):97-103; Palmero EI et al. Sci. Rep. 2018 Jun;8(1):9188). Of note, this alteration is also designated as 5909insA in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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 Color Diagnostics, LLC DBA Color Health, SCV000911073.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This variant inserts 1 nucleotide in exon 11 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with breast or ovarian cancer (PMID: 16683254, 17851763, 27153395, 27463008, 28294317, 28724667, 28993434, 29907814). This variant has been identified in 1/250446 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

#	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: Jun 2, 2024

ClinVar

Relating variation to medicine