NM_000059.4(BRCA2):c.572A>G (p.Asp191Gly) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 17, 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:: RCV003162382.2

Allele description [Variation Report for NM_000059.4(BRCA2):c.572A>G (p.Asp191Gly)]

NM_000059.4(BRCA2):c.572A>G (p.Asp191Gly)

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.572A>G (p.Asp191Gly)

HGVS:

NC_000013.11:g.32326554A>G
NG_012772.3:g.16075A>G
NM_000059.4:c.572A>GMANE SELECT
NP_000050.2:p.Asp191Gly
NP_000050.3:p.Asp191Gly
LRG_293t1:c.572A>G
LRG_293:g.16075A>G
LRG_293p1:p.Asp191Gly
NC_000013.10:g.32900691A>G
NM_000059.3:c.572A>G

Protein change:

D191G

Links:

dbSNP: rs397507798

NCBI 1000 Genomes Browser:

rs397507798

Molecular consequence:

NM_000059.4:c.572A>G - 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
SCV003853788	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jan 17, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22962691, 30883759 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003853788

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jan 17, 2023)

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

Multiple sequence variants of BRCA2 exon 7 alter splicing regulation.

Gaildrat P, Krieger S, Di Giacomo D, Abdat J, Révillion F, Caputo S, Vaur D, Jamard E, Bohers E, Ledemeney D, Peyrat JP, Houdayer C, Rouleau E, Lidereau R, Frébourg T, Hardouin A, Tosi M, Martins A.

J Med Genet. 2012 Oct;49(10):609-17. doi: 10.1136/jmedgenet-2012-100965. Epub 2012 Sep 7.

PubMed [citation]

PMID:: 22962691

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, SCV003853788.2

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

Description

The c.572A>G variant (also known as p.D191G), located in coding exon 6 of the BRCA2 gene, results from an A to G substitution at nucleotide position 572. RNA studies have demonstrated that this alteration results in abnormal splicing that results in the in-frame loss of 20 amino acids (Ambry internal data; Gaildrat P et al. J Med Genet, 2012 Oct;49:609-17; Fraile-Bethencourt E et al. J Pathol, 2019 Aug;248:409-420); however, the exact functional impact of the deleted amino acids is unknown at this time. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice donor site. 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 8, 2024

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