chr13-32385062-C-T

Variant names:

• chr13-32385062-C-T
• rs2238162
• NM_000059.4:c.9256+4917C>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.9256+4917C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 296,974 control chromosomes in the GnomAD database, including 40,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

• Frequency:
  • Genomes: 𝑓 0.52 (20424 hom., cov: 32)
  • Exomes 𝑓: 0.53 (20280 hom.)
• Consequence: BRCA2 NM_000059.4 intron
• Clinical Significance: Benign reviewed by expert panel B:2
• Conservation: PhyloP100: -0.336
• Publications: 10 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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 13-32385062-C-T is Benign according to our data. Variant chr13-32385062-C-T is described in ClinVar as Benign. ClinVar VariationId is 209952.Status of the report is reviewed_by_expert_panel, 3 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 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.9256+4917C>T		intron	N/A	NP_000050.3	A0A7P0T9D7
	BRCA2	NM_001432077.1		c.9256+4917C>T		intron	N/A	NP_001419006.1	A0A7P0T9D7
	BRCA2	NM_001406720.1		c.9205+4917C>T		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+4917C>T		intron	N/A	ENSP00000369497.3	P51587
	BRCA2	ENST00000544455.6	TSL:1	c.9256+4917C>T		intron	N/A	ENSP00000439902.1	P51587
	BRCA2	ENST00000530893.7	TSL:1	c.8887+4917C>T		intron	N/A	ENSP00000499438.2	A0A590UJI7

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78539 AN: 151896 Hom.: 20404 Cov.: 32

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.527 AC: 76373 AN: 144960 Hom.: 20280 Cov.: 0 AF XY: 0.522 AC XY: 39989 AN XY: 76534

African (AFR) AF: 0.506 AC: 2090 AN: 4134

American (AMR) AF: 0.506 AC: 4393 AN: 8680

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1873 AN: 3928

East Asian (EAS) AF: 0.609 AC: 5785 AN: 9498

South Asian (SAS) AF: 0.476 AC: 3082 AN: 6470

European-Finnish (FIN) AF: 0.577 AC: 14050 AN: 24332

Middle Eastern (MID) AF: 0.381 AC: 697 AN: 1830

European-Non Finnish (NFE) AF: 0.515 AC: 40315 AN: 78216

Other (OTH) AF: 0.519 AC: 4088 AN: 7872

GnomAD4 genome AF: 0.517 AC: 78610 AN: 152014 Hom.: 20424 Cov.: 32 AF XY: 0.521 AC XY: 38698 AN XY: 74294

African (AFR) AF: 0.500 AC: 20717 AN: 41454

American (AMR) AF: 0.529 AC: 8084 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1639 AN: 3470

East Asian (EAS) AF: 0.570 AC: 2943 AN: 5162

South Asian (SAS) AF: 0.479 AC: 2309 AN: 4820

European-Finnish (FIN) AF: 0.573 AC: 6057 AN: 10566

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35295 AN: 67952

Other (OTH) AF: 0.498 AC: 1053 AN: 2114

Alfa AF: 0.518 Hom.: 2635

Bravo AF: 0.510

Asia WGS AF: 0.521 AC: 1812 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	1	Breast-ovarian cancer, familial, susceptibility to, 2 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.69
DANN	Benign	0.44
PhyloP100		-0.34
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: rs2238162; hg19: chr13-32959199;