rs189026060
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000059.4(BRCA2):c.67+82C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00338 in 1,188,390 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Genomes: 𝑓 0.0028 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0035 ( 17 hom. )
Consequence
BRCA2
NM_000059.4 intron
NM_000059.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.73
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 Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 13-32316609-C-G is Benign according to our data. Variant chr13-32316609-C-G is described in ClinVar as [Benign]. Clinvar id is 52164.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32316609-C-G is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00347 (3593/1036354) while in subpopulation MID AF= 0.0152 (55/3614). AF 95% confidence interval is 0.012. There are 17 homozygotes in gnomad4_exome. There are 1920 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 17 AD,AR gene
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| BRCA2 | ENST00000380152.8 | c.67+82C>G | intron_variant | Intron 2 of 26 | 5 | NM_000059.4 | ENSP00000369497.3 | |||
| BRCA2 | ENST00000530893.7 | c.-303+86C>G | intron_variant | Intron 2 of 26 | 1 | ENSP00000499438.2 | ||||
| BRCA2 | ENST00000614259.2 | n.67+82C>G | intron_variant | Intron 1 of 25 | 2 | ENSP00000506251.1 |
Frequencies
GnomAD3 genomes 0.00281 AC: 427AN: 151918Hom.: 1 Cov.: 33
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GnomAD4 exome AF: 0.00347 AC: 3593AN: 1036354Hom.: 17 AF XY: 0.00363 AC XY: 1920AN XY: 528420
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GnomAD4 genome 0.00281 AC: 427AN: 152036Hom.: 1 Cov.: 33 AF XY: 0.00258 AC XY: 192AN XY: 74304
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ClinVar
Significance: Benign
Submissions summary: Uncertain:2Benign:5
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
not provided Benign:3
-
Genome Diagnostics Laboratory, University Medical Center Utrecht
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
- -
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Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
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Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided
- -
Breast-ovarian cancer, familial, susceptibility to, 2 Uncertain:1Benign:1
Dec 17, 2010
Breast Cancer Information Core (BIC) (BRCA2)
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: clinical testing
- -
Jun 18, 2019
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Significance: Benign
Review Status: reviewed by expert panel
Collection Method: curation
IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 7.82E-136 -
Hereditary cancer-predisposing syndrome Uncertain:1
Feb 04, 2016
Vantari Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Hereditary breast ovarian cancer syndrome Benign:1
Oct 29, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at