13-32399139-A-C

Variant names:

• chr13-32399139-A-C
• rs7334543
• ENST00000614259.2:n.*2684A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000614259.2(BRCA2):​n.*2684A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BRCA2 ENST00000614259.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 0 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):

• breast-ovarian cancer, familial, susceptibility to, 2

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

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, G2P
• 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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRCA2	NM_000059.4	c.*369A>C		3_prime_UTR_variant	Exon 27 of 27	ENST00000380152.8	NP_000050.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRCA2	ENST00000614259.2	n.*2684A>C		non_coding_transcript_exon_variant	Exon 26 of 26	2		ENSP00000506251.1
BRCA2	ENST00000380152.8	c.*369A>C		3_prime_UTR_variant	Exon 27 of 27	5	NM_000059.4	ENSP00000369497.3
BRCA2	ENST00000530893.7	c.*369A>C		3_prime_UTR_variant	Exon 27 of 27	1		ENSP00000499438.2
BRCA2	ENST00000614259.2	n.*2684A>C		3_prime_UTR_variant	Exon 26 of 26	2		ENSP00000506251.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 79866 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 37978

African (AFR) AF: 0.00 AC: 0 AN: 3154

American (AMR) AF: 0.00 AC: 0 AN: 2950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4370

East Asian (EAS) AF: 0.00 AC: 0 AN: 10124

South Asian (SAS) AF: 0.00 AC: 0 AN: 2028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 818

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 466

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 49656

Other (OTH) AF: 0.00 AC: 0 AN: 6300

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.6
DANN	Benign	0.89
PhyloP100		-0.045

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;