rs7334543

Variant names:

• chr13-32399139-A-G
• rs7334543
• NM_000059.4:c.*369A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-32399139-A-G
• chr13-32399139-A-C
• chr13-32399139-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000059.4(BRCA2):​c.*369A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 231,366 control chromosomes in the GnomAD database, including 7,970 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★). The gene BRCA2 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.27 (5789 hom., cov: 30)
  • Exomes 𝑓: 0.20 (2181 hom.)
• Consequence: BRCA2 NM_000059.4 3_prime_UTR
• Clinical Significance: Benign reviewed by expert panel B:6
• Conservation: PhyloP100: -0.0450
• Publications: 13 publications found

Genes affected

BRCA2 (HGNC:1101): (BRCA2 DNA repair associated) Inherited mutations in BRCA1 and this gene, BRCA2, confer increased lifetime risk of developing breast or ovarian cancer. Both BRCA1 and BRCA2 are involved in maintenance of genome stability, specifically the homologous recombination pathway for double-strand DNA repair. The largest exon in both genes is exon 11, which harbors the most important and frequent mutations in breast cancer patients. The BRCA2 gene was found on chromosome 13q12.3 in human. The BRCA2 protein contains several copies of a 70 aa motif called the BRC motif, and these motifs mediate binding to the RAD51 recombinase which functions in DNA repair. BRCA2 is considered a tumor suppressor gene, as tumors with BRCA2 mutations generally exhibit loss of heterozygosity (LOH) of the wild-type allele. [provided by RefSeq, May 2020]

BRCA2 Gene-Disease associations (from GenCC):

• BRCA2-related cancer predisposition

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• breast-ovarian cancer, familial, susceptibility to, 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• Fanconi anemia complementation group D1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• pancreatic cancer, susceptibility to, 2

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• sarcoma

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• hereditary breast ovarian cancer syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• medulloblastoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Specifications for BRCA2 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 13-32399139-A-G is Benign according to our data. Variant chr13-32399139-A-G is described in ClinVar as Benign. ClinVar VariationId is 209924.Status of the report is reviewed_by_expert_panel, 3 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000059.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRCA2	NM_000059.4	MANE Select	c.*369A>G		3_prime_UTR	Exon 27 of 27	NP_000050.3	A0A7P0T9D7
	BRCA2	NM_001432077.1		c.*369A>G		3_prime_UTR	Exon 27 of 27	NP_001419006.1	A0A7P0T9D7
	BRCA2	NM_001406720.1		c.*369A>G		3_prime_UTR	Exon 27 of 27	NP_001393649.1	A0A8V8TPZ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRCA2	ENST00000380152.8	TSL:5 MANE Select	c.*369A>G		3_prime_UTR	Exon 27 of 27	ENSP00000369497.3	P51587
	BRCA2	ENST00000544455.6	TSL:1	c.*369A>G		3_prime_UTR	Exon 27 of 27	ENSP00000439902.1	P51587
	BRCA2	ENST00000530893.7	TSL:1	c.*369A>G		3_prime_UTR	Exon 27 of 27	ENSP00000499438.2	A0A590UJI7

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40817 AN: 151510 Hom.: 5784 Cov.: 30

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0749

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.203 AC: 16204 AN: 79740 Hom.: 2181 Cov.: 0 AF XY: 0.200 AC XY: 7567 AN XY: 37906

African (AFR) AF: 0.287 AC: 902 AN: 3144

American (AMR) AF: 0.210 AC: 619 AN: 2948

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 868 AN: 4358

East Asian (EAS) AF: 0.0362 AC: 366 AN: 10124

South Asian (SAS) AF: 0.0944 AC: 191 AN: 2024

European-Finnish (FIN) AF: 0.211 AC: 172 AN: 814

Middle Eastern (MID) AF: 0.131 AC: 61 AN: 466

European-Non Finnish (NFE) AF: 0.234 AC: 11599 AN: 49566

Other (OTH) AF: 0.226 AC: 1426 AN: 6296

GnomAD4 genome AF: 0.270 AC: 40865 AN: 151626 Hom.: 5789 Cov.: 30 AF XY: 0.266 AC XY: 19677 AN XY: 74054

African (AFR) AF: 0.308 AC: 12724 AN: 41318

American (AMR) AF: 0.253 AC: 3858 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 756 AN: 3470

East Asian (EAS) AF: 0.0753 AC: 390 AN: 5180

South Asian (SAS) AF: 0.158 AC: 756 AN: 4794

European-Finnish (FIN) AF: 0.315 AC: 3285 AN: 10442

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18299 AN: 67846

Other (OTH) AF: 0.239 AC: 505 AN: 2112

Alfa AF: 0.273 Hom.: 2065

Bravo AF: 0.267

Asia WGS AF: 0.155 AC: 536 AN: 3468

ClinVar

ClinVar submissions

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	2	Breast-ovarian cancer, familial, susceptibility to, 2 (2)
-	-	1	Fanconi anemia complementation group D1 (1)
-	-	1	Hereditary cancer-predisposing syndrome (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.8
DANN	Benign	0.90
PhyloP100		-0.045
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7334543; hg19: chr13-32973276;