NM_000059.4(BRCA2):c.67G>A (p.Asp23Asn) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 8, 2023
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:: RCV003343705.2

Allele description [Variation Report for NM_000059.4(BRCA2):c.67G>A (p.Asp23Asn)]

NM_000059.4(BRCA2):c.67G>A (p.Asp23Asn)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.67G>A (p.Asp23Asn)

HGVS:

NC_000013.11:g.32316527G>A
NG_012772.3:g.6048G>A
NG_017006.2:g.3837C>T
NM_000059.4:c.67G>AMANE SELECT
NP_000050.2:p.Asp23Asn
NP_000050.3:p.Asp23Asn
LRG_293t1:c.67G>A
LRG_293:g.6048G>A
LRG_293p1:p.Asp23Asn
NC_000013.10:g.32890664G>A
NG_017006.1:g.428C>T
NM_000059.3:c.67G>A

Protein change:

D23N

Links:

dbSNP: rs397507881

NCBI 1000 Genomes Browser:

rs397507881

Molecular consequence:

NM_000059.4:c.67G>A - missense variant - [Sequence Ontology: SO:0001583]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004052581	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Aug 8, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004052581

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Aug 8, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Mis-splicing in breast cancer: identification of pathogenic BRCA2 variants by systematic minigene assays.

Fraile-Bethencourt E, Valenzuela-Palomo A, Díez-Gómez B, Goina E, Acedo A, Buratti E, Velasco EA.

J Pathol. 2019 Aug;248(4):409-420. doi: 10.1002/path.5268. Epub 2019 Apr 23.

PubMed [citation]

PMID:: 30883759

Details of each submission

From Ambry Genetics, SCV004052581.2

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

Description

The c.67G>A variant (also known as p.D23N), located in coding exon 1 of the BRCA2 gene, results from a G to A substitution at nucleotide position 67. The amino acid change results in aspartic acid to asparagine at codon 23, an amino acid with highly similar properties. However, this change occurs in the last base pair of coding exon 1, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. RNA studies have shown this alteration to result in a novel donor gain which causes a frameshift (Ambry internal data; Fraile-Bethencourt, E et al. J Pathol 2019 Aug;248(4):409-420). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Sep 29, 2024

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