13-32386106-C-A

Variant names:

• chr13-32386106-C-A
• rs182035795
• NM_000059.4:c.9256+5961C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_000059.4(BRCA2):​c.9256+5961C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 175,752 control chromosomes in the GnomAD database, including 1 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 0.0018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00051 (0 hom.)
• Consequence: BRCA2 NM_000059.4 intron
• Clinical Significance: Benign reviewed by expert panel B:1
• Conservation: PhyloP100: -0.391
• 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]

IFIT1P1 (HGNC:5408): (interferon induced protein with tetratricopeptide repeats 1 pseudogene 1)

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 13-32386106-C-A is Benign according to our data. Variant chr13-32386106-C-A is described in ClinVar as Benign. ClinVar VariationId is 264945.Status of the report is reviewed_by_expert_panel, 3 stars.

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.9256+5961C>A		intron	N/A	NP_000050.3	A0A7P0T9D7
	BRCA2	NM_001432077.1		c.9256+5961C>A		intron	N/A	NP_001419006.1	A0A7P0T9D7
	BRCA2	NM_001406720.1		c.9205+5961C>A		intron	N/A	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.9256+5961C>A		intron	N/A	ENSP00000369497.3	P51587
	BRCA2	ENST00000544455.6	TSL:1	c.9256+5961C>A		intron	N/A	ENSP00000439902.1	P51587
	BRCA2	ENST00000530893.7	TSL:1	c.8887+5961C>A		intron	N/A	ENSP00000499438.2	A0A590UJI7

Frequencies

GnomAD3 genomes AF: 0.00180 AC: 274 AN: 152140 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00635

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.000511 AC: 12 AN: 23494 Hom.: 0 Cov.: 0 AF XY: 0.000303 AC XY: 4 AN XY: 13188

African (AFR) AF: 0.00831 AC: 11 AN: 1324

American (AMR) AF: 0.00 AC: 0 AN: 2632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 284

East Asian (EAS) AF: 0.00 AC: 0 AN: 2660

South Asian (SAS) AF: 0.00 AC: 0 AN: 2330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1614

Middle Eastern (MID) AF: 0.000867 AC: 1 AN: 1154

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 10470

Other (OTH) AF: 0.00 AC: 0 AN: 1026

GnomAD4 genome AF: 0.00181 AC: 275 AN: 152258 Hom.: 1 Cov.: 32 AF XY: 0.00176 AC XY: 131 AN XY: 74434

African (AFR) AF: 0.00635 AC: 264 AN: 41556

American (AMR) AF: 0.000588 AC: 9 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68008

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00166 Hom.: 0

Bravo AF: 0.00223

ClinVar

ClinVar submissions

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	1	Breast-ovarian cancer, familial, susceptibility to, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.5
DANN	Benign	0.93
PhyloP100		-0.39

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: rs182035795; hg19: chr13-32960243;