rs545321666

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS1

The NM_000059.4(BRCA2):​c.-59_-57del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000709 in 152,332 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.00071 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

BRCA2
NM_000059.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign reviewed by expert panel U:1B:4

Conservation

PhyloP100: 0.0270
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6
Variant 13-32315645-AAAG-A is Benign according to our data. Variant chr13-32315645-AAAG-A is described in ClinVar as [Benign]. Clinvar id is 264878.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32315645-AAAG-A is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000709 (108/152332) while in subpopulation SAS AF= 0.0217 (105/4832). AF 95% confidence interval is 0.0184. There are 0 homozygotes in gnomad4. There are 81 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BRCA2NM_000059.4 linkuse as main transcriptc.-59_-57del 5_prime_UTR_variant 1/27 ENST00000380152.8 NP_000050.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BRCA2ENST00000380152.8 linkuse as main transcriptc.-59_-57del 5_prime_UTR_variant 1/275 NM_000059.4 ENSP00000369497 A2

Frequencies

GnomAD3 genomes
AF:
0.000696
AC:
106
AN:
152214
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000578
Gnomad SAS
AF:
0.0213
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
112
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
76
Gnomad4 AFR exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000709
AC:
108
AN:
152332
Hom.:
0
Cov.:
33
AF XY:
0.00109
AC XY:
81
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000580
Gnomad4 SAS
AF:
0.0217
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000285
Hom.:
0
Bravo
AF:
0.000144
Asia WGS
AF:
0.00924
AC:
32
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Uncertain:1Benign:4
Revision: reviewed by expert panel
LINK: link

Submissions by phenotype

Hereditary breast ovarian cancer syndrome Benign:2
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoOct 31, 2018- -
Breast-ovarian cancer, familial, susceptibility to, 2 Benign:1
Benign, reviewed by expert panelcurationEvidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)Sep 28, 2016Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.0307 (South Asian), derived from 1000 genomes (2013-05-02). -
Fanconi anemia Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs545321666; hg19: chr13-32889782; API