2-214728537-C-CTTT
Variant summary
Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong
The NM_000465.4(BARD1):c.*136_*138dupAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.018 ( 39 hom., cov: 0)
Exomes 𝑓: 0.023 ( 7 hom. )
Failed GnomAD Quality Control
Consequence
BARD1
NM_000465.4 3_prime_UTR
NM_000465.4 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.392
Publications
1 publications found
Genes affected
BARD1 (HGNC:952): (BRCA1 associated RING domain 1) This gene encodes a protein which interacts with the N-terminal region of BRCA1. In addition to its ability to bind BRCA1 in vivo and in vitro, it shares homology with the 2 most conserved regions of BRCA1: the N-terminal RING motif and the C-terminal BRCT domain. The RING motif is a cysteine-rich sequence found in a variety of proteins that regulate cell growth, including the products of tumor suppressor genes and dominant protooncogenes. This protein also contains 3 tandem ankyrin repeats. The BARD1/BRCA1 interaction is disrupted by tumorigenic amino acid substitutions in BRCA1, implying that the formation of a stable complex between these proteins may be an essential aspect of BRCA1 tumor suppression. This protein may be the target of oncogenic mutations in breast or ovarian cancer. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]
BARD1 Gene-Disease associations (from GenCC):
- breast cancerInheritance: AD Classification: DEFINITIVE Submitted by: G2P
- hereditary breast carcinomaInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
- familial ovarian cancerInheritance: AD Classification: LIMITED Submitted by: ClinGen
- hereditary nonpolyposis colon cancerInheritance: AD Classification: LIMITED Submitted by: ClinGen
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -8 ACMG points.
BP6
Variant 2-214728537-C-CTTT is Benign according to our data. Variant chr2-214728537-C-CTTT is described in ClinVar as [Likely_benign]. Clinvar id is 801874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0182 AC: 2620AN: 143954Hom.: 39 Cov.: 0 show subpopulations
GnomAD3 genomes
AF:
AC:
2620
AN:
143954
Hom.:
Cov.:
0
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0228 AC: 10091AN: 441932Hom.: 7 Cov.: 6 AF XY: 0.0226 AC XY: 5176AN XY: 229074 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
10091
AN:
441932
Hom.:
Cov.:
6
AF XY:
AC XY:
5176
AN XY:
229074
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
190
AN:
11894
American (AMR)
AF:
AC:
232
AN:
14908
Ashkenazi Jewish (ASJ)
AF:
AC:
343
AN:
12272
East Asian (EAS)
AF:
AC:
155
AN:
27030
South Asian (SAS)
AF:
AC:
818
AN:
33554
European-Finnish (FIN)
AF:
AC:
639
AN:
24382
Middle Eastern (MID)
AF:
AC:
35
AN:
2304
European-Non Finnish (NFE)
AF:
AC:
7146
AN:
291462
Other (OTH)
AF:
AC:
533
AN:
24126
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.338
Heterozygous variant carriers
0
664
1328
1992
2656
3320
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0182 AC: 2618AN: 143982Hom.: 39 Cov.: 0 AF XY: 0.0168 AC XY: 1169AN XY: 69640 show subpopulations
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
2618
AN:
143982
Hom.:
Cov.:
0
AF XY:
AC XY:
1169
AN XY:
69640
show subpopulations
African (AFR)
AF:
AC:
222
AN:
39442
American (AMR)
AF:
AC:
191
AN:
14556
Ashkenazi Jewish (ASJ)
AF:
AC:
127
AN:
3420
East Asian (EAS)
AF:
AC:
8
AN:
4986
South Asian (SAS)
AF:
AC:
67
AN:
4570
European-Finnish (FIN)
AF:
AC:
141
AN:
7678
Middle Eastern (MID)
AF:
AC:
6
AN:
284
European-Non Finnish (NFE)
AF:
AC:
1769
AN:
66162
Other (OTH)
AF:
AC:
43
AN:
1980
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
111
222
334
445
556
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Aug 14, 2019
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Familial cancer of breast Benign:1
May 28, 2019
Mendelics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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