NM_000059.4(BRCA2):c.6445_6446del (p.Ser2148_Ile2149insTer) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 28, 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:: RCV002362669.9

Allele description [Variation Report for NM_000059.4(BRCA2):c.6445_6446del (p.Ser2148_Ile2149insTer)]

NM_000059.4(BRCA2):c.6445_6446del (p.Ser2148_Ile2149insTer)

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.6445_6446del (p.Ser2148_Ile2149insTer)

HGVS:

NC_000013.11:g.32340800_32340801del
NG_012772.3:g.30321_30322del
NM_000059.4:c.6445_6446delMANE SELECT
NP_000050.3:p.Ser2148_Ile2149insTer
LRG_293:g.30321_30322del
NC_000013.10:g.32914936_32914937del
NC_000013.10:g.32914937_32914938del
NM_000059.3:c.6445_6446delAT
NM_000059.4:c.6445_6446del
U43746.1:n.6673_6674delAT

Nucleotide change:

6673delAT

Links:

Breast Cancer Information Core (BIC) (BRCA2): 6673&base_change=del AT; dbSNP: rs80359592

NCBI 1000 Genomes Browser:

rs80359592

Molecular consequence:

NM_000059.4:c.6445_6446del - nonsense - [Sequence Ontology: SO:0001587]

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

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Dickeya dadantii strain CFBP 6467 DnaA (dnaA) gene, partial cds
Dickeya dadantii strain CFBP 6467 DnaA (dnaA) gene, partial cds
gi|484353660|gb|JX434881.1|

Nucleotide
Bacillus sp. (in: firmicutes) 16S ribosomal RNA gene, partial sequence
Bacillus sp. (in: firmicutes) 16S ribosomal RNA gene, partial sequence
gi|1102130585|gb|KY119378.1|

Nucleotide
Grania chilensis isolate PDW193 12S ribosomal RNA gene, partial sequence; mitoch...
Grania chilensis isolate PDW193 12S ribosomal RNA gene, partial sequence; mitochondrial
gi|326578331|gb|GU902127.1|

Nucleotide
Acronyms and Abbreviations - Use of Glycated Hemoglobin and Microalbuminuria in ...
Acronyms and Abbreviations - Use of Glycated Hemoglobin and Microalbuminuria in the Monitoring of Diabetes Mellitus
AKR1 palmitoyltransferase AKR1 [Saccharomyces cerevisiae S288C]
AKR1 palmitoyltransferase AKR1 [Saccharomyces cerevisiae S288C]
Gene ID:851857

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002657448	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Mar 28, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19016756, 33891299 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002657448

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Mar 28, 2022)

germline

clinical testing

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

Citation Link

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

Cross-sectional analysis of germline BRCA1 and BRCA2 mutations in Japanese patients suspected to have hereditary breast/ovarian cancer.

Sugano K, Nakamura S, Ando J, Takayama S, Kamata H, Sekiguchi I, Ubukata M, Kodama T, Arai M, Kasumi F, Hirai Y, Ikeda T, Jinno H, Kitajima M, Aoki D, Hirasawa A, Takeda Y, Yazaki K, Fukutomi T, Kinoshita T, Tsunematsu R, Yoshida T, et al.

Cancer Sci. 2008 Oct;99(10):1967-76. doi: 10.1111/j.1349-7006.2008.00944.x.

PubMed [citation]

PMID:: 19016756
PMCID:: PMC11158907

Genetic testing results in Slovenian male breast cancer cohort indicate the BRCA2 7806-2A > G founder variant could be associated with higher male breast cancer risk.

Strojnik K, Krajc M, Dragos VS, Stegel V, Novakovic S, Blatnik A.

Breast Cancer Res Treat. 2021 Aug;188(3):811-820. doi: 10.1007/s10549-021-06224-5. Epub 2021 Apr 23.

PubMed [citation]

PMID:: 33891299
PMCID:: PMC8272709

Details of each submission

From Ambry Genetics, SCV002657448.2

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

Description

The c.6445_6446delAT pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 6445 to 6446, causing a translational frameshift with a predicted alternate stop codon (p.I2149*). This alteration has been identified in multiple individuals diagnosed with breast cancer (Sugano K et al. Cancer Sci, 2008 Oct;99:1967-76; Strojnik K et al. Breast Cancer Res Treat, 2021 Aug;188:811-820). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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

Last Updated: Nov 3, 2024

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