NM_000059.4(BRCA2):c.700del (p.Ser234fs) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 3, 2019
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:: RCV000486024.12

Allele description

NM_000059.4(BRCA2):c.700del (p.Ser234fs)

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.700del (p.Ser234fs)

Other names:

924delT

HGVS:

NC_000013.11:g.32330937del
NG_012772.3:g.20458del
NM_000059.4:c.700delMANE SELECT
NP_000050.3:p.Ser234fs
LRG_293t1:c.700del
LRG_293:g.20458del
NC_000013.10:g.32905070del
NC_000013.10:g.32905074del
NM_000059.3:c.696delT
NM_000059.3:c.700delT
U43746.1:n.928delT
p.Ser234Profs*7

Nucleotide change:

928delT

Links:

Breast Cancer Information Core (BIC) (BRCA2): 924&base_change=del T; Breast Cancer Information Core (BIC) (BRCA2): 928&base_change=del T; dbSNP: rs80359630

NCBI 1000 Genomes Browser:

rs80359630

Molecular consequence:

NM_000059.4:c.700del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Homo sapiens fatty acid binding protein 12 (FABP12), transcript variant 1, mRNA
Homo sapiens fatty acid binding protein 12 (FABP12), transcript variant 1, mRNA
gi|2450651315|ref|NM_001105281.6|

Nucleotide
Homo sapiens fatty acid binding protein 12 (FABP12), transcript variant 2, non-c...
Homo sapiens fatty acid binding protein 12 (FABP12), transcript variant 2, non-coding RNA
gi|1070257842|ref|NR_144370.1|

Nucleotide
DQM35_RS09105 [Streptococcus pyogenes]
DQM35_RS09105 [Streptococcus pyogenes]
Gene ID:69901672

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000568443	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Dec 3, 2019)	germline	clinical testing	Citation Link,
SCV000591708	Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR) See additional submitters Franklin by Genoox	no assertion criteria provided	Pathogenic	unknown	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000568443

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Dec 3, 2019)

germline

clinical testing

Citation Link,

SCV000591708

Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided

Pathogenic

unknown

clinical testing

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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	clinical testing
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000568443.5

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

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Observed in individuals with BRCA2-related cancers (Nedelcu 2002, Lubinski 2004, Giannini 2006, Sinilnikova 2006, Seong 2009, Kim 2012, Germani 2018; Also known as 924delT and 928delT; This variant is associated with the following publications: (PMID: 15131399, 11938448, 16847550, 16528604, 26843898, 22798144, 19656164, 25948282, 22762150, 30263092, 31921681)

#	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 Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV000591708.2

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

Description

The p.Ser234ProfsX7 deletion variant was identified in 4 of 6352 proband chromosomes (frequency: 0.001) from individuals or families with breast or ovarian cancer (Capalbo 2006, Kim 2012, Meindl 2002, Nedelcu 2002). The variant was also identified in dbSNP (ID: rs80359630) â€šÃ„ÃºWith Pathogenic alleleâ€šÃ„Ã¹, HGMD, ClinVar database, the BIC database (3X with clinical importance), and UMD (6X as a causal variant). The variant was classified as a pathogenic variant by the Sharing Clinical Reports Project (SCRP) (submitted within the ClinVar database and derived from Myriad reports). The p.Ser234ProfsX7 deletion variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 234 and leads to a premature stop codon 7 codons downstream. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the BRCA2 gene are an established mechanism of disease in hereditary breast and ovarian cancer and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratoryâ€šÃ„Ã´s criteria to be classified as pathogenic.

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

Last Updated: Jun 17, 2024

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