rs2238163

Variant names:

• chr13-32385702-A-C
• rs2238163
• NM_000059.4:c.9256+5557A>C

Your query was ambiguous. Multiple possible variants found:

• chr13-32385702-A-C
• chr13-32385702-A-G
• chr13-32385702-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.9256+5557A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 195,738 control chromosomes in the GnomAD database, including 26,918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

• Frequency:
  • Genomes: 𝑓 0.52 (20422 hom., cov: 32)
  • Exomes 𝑓: 0.55 (6496 hom.)
• Consequence: BRCA2 NM_000059.4 intron
• Clinical Significance: Benign reviewed by expert panel B:2
• Conservation: PhyloP100: 0.0560
• Publications: 7 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=-0.91).
• BP6: Variant 13-32385702-A-C is Benign according to our data. Variant chr13-32385702-A-C is described in ClinVar as Benign. ClinVar VariationId is 209953.Status of the report is reviewed_by_expert_panel, 3 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 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+5557A>C		intron	N/A	NP_000050.3	A0A7P0T9D7
	BRCA2	NM_001432077.1		c.9256+5557A>C		intron	N/A	NP_001419006.1	A0A7P0T9D7
	BRCA2	NM_001406720.1		c.9205+5557A>C		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+5557A>C		intron	N/A	ENSP00000369497.3	P51587
	BRCA2	ENST00000544455.6	TSL:1	c.9256+5557A>C		intron	N/A	ENSP00000439902.1	P51587
	BRCA2	ENST00000530893.7	TSL:1	c.8887+5557A>C		intron	N/A	ENSP00000499438.2	A0A590UJI7

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78523 AN: 151860 Hom.: 20402 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.547 AC: 23938 AN: 43760 Hom.: 6496 Cov.: 0 AF XY: 0.545 AC XY: 13796 AN XY: 25330

African (AFR) AF: 0.554 AC: 288 AN: 520

American (AMR) AF: 0.566 AC: 1810 AN: 3200

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 350 AN: 686

East Asian (EAS) AF: 0.627 AC: 943 AN: 1504

South Asian (SAS) AF: 0.523 AC: 2328 AN: 4448

European-Finnish (FIN) AF: 0.596 AC: 3166 AN: 5308

Middle Eastern (MID) AF: 0.378 AC: 657 AN: 1740

European-Non Finnish (NFE) AF: 0.545 AC: 13195 AN: 24196

Other (OTH) AF: 0.557 AC: 1201 AN: 2158

GnomAD4 genome AF: 0.517 AC: 78594 AN: 151978 Hom.: 20422 Cov.: 32 AF XY: 0.521 AC XY: 38679 AN XY: 74272

African (AFR) AF: 0.500 AC: 20700 AN: 41426

American (AMR) AF: 0.530 AC: 8093 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1636 AN: 3468

East Asian (EAS) AF: 0.569 AC: 2935 AN: 5154

South Asian (SAS) AF: 0.479 AC: 2302 AN: 4806

European-Finnish (FIN) AF: 0.572 AC: 6047 AN: 10566

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

European-Non Finnish (NFE) AF: 0.520 AC: 35314 AN: 67958

Other (OTH) AF: 0.498 AC: 1052 AN: 2114

Alfa AF: 0.392 Hom.: 1117

Bravo AF: 0.511

Asia WGS AF: 0.521 AC: 1811 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	-0.91
CADD	Benign	0.38
DANN	Benign	0.73
PhyloP100		0.056
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: rs2238163; hg19: chr13-32959839; COSMIC: COSV66457900;