rs1060504610
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_000059.4(BRCA2):c.7805+11C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
BRCA2
NM_000059.4 intron
NM_000059.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0260
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 made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 13-32357940-C-A is Benign according to our data. Variant chr13-32357940-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 415653.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1, Benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRCA2 | NM_000059.4 | c.7805+11C>A | intron_variant | ENST00000380152.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRCA2 | ENST00000380152.8 | c.7805+11C>A | intron_variant | 5 | NM_000059.4 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251144Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135778
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GnomAD4 exome AF: 0.00000343 AC: 5AN: 1458766Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2AN XY: 725922
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 24, 2017 | Variant summary: c.7805+11C>A in the BRCA2 gene is an intronic change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict this variant does not affect a normal splicing pattern, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of gnomAD at frequency of 0.000008 (2/245950 chrs tested). The observed frequency does not exceed the maximum expected allele frequency for a pathogenic variant of 0.00075. The variant of interest has been cited by a clinical laboratory as Likely Benign. Taken together, the variant is classified as VUS-Possibly Benign until additional information becomes available. - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Apr 27, 2016 | - - |
Hereditary breast ovarian cancer syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at