NM_000059.4:c.9256+4541G>A
Variant names:
Variant summary
Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_000059.4(BRCA2):c.9256+4541G>A variant causes a intron 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. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
BRCA2
NM_000059.4 intron
NM_000059.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0540
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]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -10 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 13-32384686-G-A is Benign according to our data. Variant chr13-32384686-G-A is described in ClinVar as Benign. ClinVar VariationId is 209865.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.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| BRCA2 | TSL:5 MANE Select | c.9256+4541G>A | intron | N/A | ENSP00000369497.3 | P51587 | |||
| BRCA2 | TSL:1 | c.9256+4541G>A | intron | N/A | ENSP00000439902.1 | P51587 | |||
| BRCA2 | TSL:1 | c.8887+4541G>A | intron | N/A | ENSP00000499438.2 | A0A590UJI7 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 80248Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 46018
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
80248
Hom.:
Cov.:
0
AF XY:
AC XY:
0
AN XY:
46018
African (AFR)
AF:
AC:
0
AN:
2034
American (AMR)
AF:
AC:
0
AN:
9152
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
1126
East Asian (EAS)
AF:
AC:
0
AN:
4280
South Asian (SAS)
AF:
AC:
0
AN:
7898
European-Finnish (FIN)
AF:
AC:
0
AN:
14550
Middle Eastern (MID)
AF:
AC:
0
AN:
1732
European-Non Finnish (NFE)
AF:
AC:
0
AN:
36496
Other (OTH)
AF:
AC:
0
AN:
2980
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Benign
Revision:reviewed by expert panel
Pathogenic
VUS
Benign
Condition
-
-
1
Breast-ovarian cancer, familial, susceptibility to, 2 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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