NM_000059.4(BRCA2):c.2845del (p.Tyr949fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 12, 2022
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:: RCV000479662.10

Allele description [Variation Report for NM_000059.4(BRCA2):c.2845del (p.Tyr949fs)]

NM_000059.4(BRCA2):c.2845del (p.Tyr949fs)

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.2845del (p.Tyr949fs)

Other names:

3073delT

HGVS:

NC_000013.11:g.32337200del
NG_012772.3:g.26721del
NM_000059.4:c.2845delMANE SELECT
NP_000050.3:p.Tyr949fs
LRG_293:g.26721del
NC_000013.10:g.32911335del
NC_000013.10:g.32911337del
NM_000059.3:c.2845delT
NM_000059.4:c.2845del
p.Tyr949fs

Links:

dbSNP: rs397507644

NCBI 1000 Genomes Browser:

rs397507644

Molecular consequence:

NM_000059.4:c.2845del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000567030	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jun 23, 2015)	germline	clinical testing	Citation Link,
SCV004219556	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Dec 12, 2022)	unknown	clinical testing	PubMed (9) [See all records that cite these PMIDs] 29907814, 30702160, 28294317, 31209999, 32190957, 29446198, 31825140, 10323242, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000567030

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Jun 23, 2015)

germline

clinical testing

Citation Link,

SCV004219556

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Dec 12, 2022)

unknown

clinical testing

PubMed (9)
[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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The germline mutational landscape of BRCA1 and BRCA2 in Brazil.

Palmero EI, Carraro DM, Alemar B, Moreira MAM, Ribeiro-Dos-Santos Â, Abe-Sandes K, Galvão HCR, Reis RM, de Pádua Souza C, Campacci N, Achatz MI, Brianese RC, da Cruz Formiga MN, Makdissi FB, Vargas FR, Evangelista Dos Santos AC, Seuanez HN, Lobo de Souza KR, Netto CBO, Santos-Silva P, da Silva GS, Burbano RMR, et al.

Sci Rep. 2018 Jun 15;8(1):9188. doi: 10.1038/s41598-018-27315-2.

PubMed [citation]

PMID:: 29907814
PMCID:: PMC6003960

Germline variation in BRCA1/2 is highly ethnic-specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients.

Bhaskaran SP, Chandratre K, Gupta H, Zhang L, Wang X, Cui J, Kim YC, Sinha S, Jiang L, Lu B, Wu X, Qin Z, Huang T, Wang SM.

Int J Cancer. 2019 Aug 15;145(4):962-973. doi: 10.1002/ijc.32176. Epub 2019 Feb 13.

PubMed [citation]

PMID:: 30702160
PMCID:: PMC6617753

See all PubMed Citations (9)

Details of each submission

From GeneDx, SCV000567030.4

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

Description

This deletion of one nucleotide in BRCA2 is denoted c.2845delT at the cDNA level and p.Tyr949MetfsX11 (Y949MfsX11) at the protein level. The normal sequence, with the base that is deleted in braces, is GGTT[T]ATGT. The deletion causes a frameshift, which changes a Tyrosine to a Methionine at codon 949, and creates a premature stop codon at position 11 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.2845delT, previously reported as 3073delT, has been observed in at least one woman with a personal and family history of breast cancer (Li 1999). we consider this variant to be pathogenic.

#	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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004219556.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

This frameshift variant alters the translational reading frame of the BRCA2 mRNA and causes the premature termination of BRCA2 protein synthesis. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in individuals with breast cancer (PMIDs: 10323242 (1999) and 28294317 (2017)), in an individual with prostate cancer (PMID: 32190957 (2020)), and in individuals with suspected breast and/or ovarian cancer (PMIDs: 29907814 (2018) and 29446198 (2018)). Based on the available information, this variant is classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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