NM_000465.4(BARD1):c.33G>T (p.Gln11His) AND not provided
- Germline classification:
- Benign/Likely benign (10 submissions)
- Last evaluated:
- Mar 1, 2024
- Review status:
- 2 stars out of maximum of 4 starscriteria provided, multiple submitters, no conflicts
- Somatic classification
of clinical impact: - None
- Review status:
- (0/4) 0 stars out of maximum of 4 starsno assertion criteria provided
- Somatic classification
of oncogenicity: - None
- Review status:
- (0/4) 0 stars out of maximum of 4 starsno assertion criteria provided
- Record status:
- current
- Accession:
- RCV000587822.30
Allele description [Variation Report for NM_000465.4(BARD1):c.33G>T (p.Gln11His)]
NM_000465.4(BARD1):c.33G>T (p.Gln11His)
- Gene:
- BARD1:BRCA1 associated RING domain 1 [Gene - OMIM - HGNC]
- Variant type:
- single nucleotide variant
- Cytogenetic location:
- 2q35
- Genomic location:
- Preferred name:
- NM_000465.4(BARD1):c.33G>T (p.Gln11His)
- Other names:
- p.Q11H:CAG>CAT
- HGVS:
- NC_000002.12:g.214809537C>A
- NG_012047.3:g.5175G>T
- NM_000465.4:c.33G>TMANE SELECT
- NM_001282543.2:c.33G>T
- NM_001282545.2:c.33G>T
- NM_001282548.2:c.33G>T
- NM_001282549.2:c.33G>T
- NP_000456.2:p.Gln11His
- NP_001269472.1:p.Gln11His
- NP_001269474.1:p.Gln11His
- NP_001269477.1:p.Gln11His
- NP_001269478.1:p.Gln11His
- LRG_297t1:c.33G>T
- LRG_297:g.5175G>T
- LRG_297p1:p.Gln11His
- NC_000002.11:g.215674261C>A
- NG_012047.2:g.5168G>T
- NM_000465.2:c.33G>T
- NM_000465.3:c.33G>T
- NR_104212.2:n.147G>T
- NR_104215.2:n.147G>T
- NR_104216.2:n.147G>T
- p.Q11H
This HGVS expression did not pass validation- Protein change:
- Q11H
- Links:
- dbSNP: rs143914387
- NCBI 1000 Genomes Browser:
- rs143914387
- Molecular consequence:
- NM_000465.4:c.33G>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001282543.2:c.33G>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001282545.2:c.33G>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001282548.2:c.33G>T - missense variant - [Sequence Ontology: SO:0001583]
- NM_001282549.2:c.33G>T - missense variant - [Sequence Ontology: SO:0001583]
- NR_104212.2:n.147G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
- NR_104215.2:n.147G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
- NR_104216.2:n.147G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
- Observations:
- 2
Condition(s)
- Synonyms:
- none provided
- Identifiers:
- MedGen: C3661900
Assertion and evidence details
Submission Accession | Submitter | Review Status (Assertion method) | Clinical Significance (Last evaluated) | Origin | Method | Citations |
---|---|---|---|---|---|---|
SCV000149542 | GeneDx | criteria provided, single submitter (GeneDx Variant Classification Process June 2021) | Likely benign (Sep 26, 2020) | germline | clinical testing | |
SCV000696772 | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) | Benign (May 3, 2016) | germline | clinical testing | PubMed (4) LabCorp Variant Classification Summary - May 2015.docx, |
SCV000806127 | PreventionGenetics, part of Exact Sciences | criteria provided, single submitter (ACMG Guidelines, 2015) | Likely benign (Jan 30, 2017) | germline | clinical testing | |
SCV000887591 | Quest Diagnostics Nichols Institute San Juan Capistrano | criteria provided, single submitter (Quest Diagnostics criteria) | Benign (Jun 22, 2022) | unknown | clinical testing | |
SCV001553371 | Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)
| no assertion criteria provided | Likely benign | unknown | clinical testing | |
SCV001799931 | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus | no assertion criteria provided | Likely benign | germline | clinical testing | |
SCV001807584 | Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus | no assertion criteria provided | Likely benign | germline | clinical testing | |
SCV001967372 | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus
| no assertion criteria provided | Likely benign | germline | clinical testing | |
SCV002009140 | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | criteria provided, single submitter (ACMG Guidelines, 2015) | Likely benign (Nov 3, 2021) | germline | clinical testing | |
SCV004151320 | CeGaT Center for Human Genetics Tuebingen | criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) | Likely benign (Mar 1, 2024) | germline | clinical testing |
Summary from all submissions
Ethnicity | Origin | Affected | Individuals | Families | Chromosomes tested | Number Tested | Family history | Method |
---|---|---|---|---|---|---|---|---|
not provided | germline | yes | 2 | not provided | not provided | not provided | not provided | clinical testing |
not provided | germline | unknown | not provided | not provided | not provided | not provided | not provided | clinical testing |
not provided | unknown | unknown | not provided | not provided | not provided | not provided | not provided | clinical testing |
not provided | unknown | yes | not provided | not provided | not provided | not provided | not provided | clinical testing |
not provided | germline | not provided | not provided | not provided | not provided | not provided | not provided | clinical testing |
Citations
PubMed
Alshatwi AA, Hasan TN, Syed NA, Shafi G, Grace BL.
PLoS One. 2012;7(10):e43939. doi: 10.1371/journal.pone.0043939. Epub 2012 Oct 9.
- PMID:
- 23056176
- PMCID:
- PMC3467277
Multigene testing of moderate-risk genes: be mindful of the missense.
Young EL, Feng BJ, Stark AW, Damiola F, Durand G, Forey N, Francy TC, Gammon A, Kohlmann WK, Kaphingst KA, McKay-Chopin S, Nguyen-Dumont T, Oliver J, Paquette AM, Pertesi M, Robinot N, Rosenthal JS, Vallee M, Voegele C, Hopper JL, Southey MC, Andrulis IL, et al.
J Med Genet. 2016 Jun;53(6):366-76. doi: 10.1136/jmedgenet-2015-103398. Epub 2016 Jan 19.
- PMID:
- 26787654
- PMCID:
- PMC4893078
Details of each submission
From GeneDx, SCV000149542.9
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | not provided |
Description
In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27978560, 28135145, 25980754, 23056176, 26898890, 26787654, 27328445, 26979391, 27621404, 27498913, 26315354, 28528518, 28873162, 27443514)
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | germline | yes | not provided | not provided | not provided | not provided | not provided | not provided | not provided |
From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000696772.1
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | PubMed (4) |
Description
Variant summary: The c.33G>T (p.Gln11His) in BARD1 gene is a missense variant involves a non-conserved nucleotide and 5/5 in silico tools predict benign outcome. The variant is present in the control population dataset of ExAC at a frequency of 0.3% (115/37748 chrs tested), being most prevalent in Europeans (12/1030chrs tested), which exceeds the maximal expected allele frequency for a non-common pathogenic BARD1 variant (0.0002188). However, ExAC include a warning note that this variant is only covered in 18874 individuals (adjusted allele number = 37748). This means that the site is covered in fewer than 80% of the individuals in ExAC, which may indicate a low-quality site.The variant has been reported in affected individuals without strong evidence for causality. The variant of interest has been reported as Likely Benign/Benign by reputable databases/clinical laboratories. Taken all together, the variant was classified as Benign.
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | germline | unknown | not provided | not provided | not provided | not provided | not provided | not provided | not provided |
From PreventionGenetics, part of Exact Sciences, SCV000806127.1
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | PubMed (1) |
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | germline | unknown | not provided | not provided | not provided | not provided | not provided | not provided | not provided |
From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000887591.4
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | PubMed (8) |
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | unknown | unknown | not provided | not provided | not provided | not provided | not provided | not provided | not provided |
From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001553371.1
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | not provided |
Description
The BARD1 p.Gln11His variant was identified in 4 of 3420 proband chromosomes (frequency: 0.001) from individuals or families with CRC and Lynch associated cancer (Pearlman 2017, Yurgelun 2015). The variant was also identified in dbSNP (ID: rs143914387) as “with other allele”, and in the ClinVar and Clinvitae databases (as benign by Invitae and likely benign by GeneDx, Ambry Genetics, Illumina Clinical Services, Counsyl, and Quest Diagnostics Nichols Institute San Juan Capistrano). The variant was also identified in the Zhejiang Colon Cancer database 1x but no clinical information was provided. The variant was not identified in the Cosmic and MutDB databases. The variant was identified in the 1000 Genomes Project in 2 of 5000 chromosomes (frequency: 0.0004) and in the NHLBI GO Exome Sequencing Project in 19 of 7906 European American alleles (freq. 0.002). In addition, the variant was identified in control databases in 344 of 213748 chromosomes (1 homozygous) at a frequency of 0.002, increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 3 of 18190 chromosomes (freq: 0.0002), Other in 16 of 5410 chromosomes (freq: 0.003), Latino in 72 of 30394 chromosomes (freq: 0.002), European Non-Finnish in 178 of 92742 chromosomes (freq: 0.002), Ashkenazi Jewish in 7 of 8982 chromosomes (freq: 0.0008), European Finnish in 57 of 16012 chromosomes (freq: 0.004), and South Asian in 11 of 26824 chromosomes (freq: 0.0004) while the variant was not observed in the East Asian population. The p.Gln11His residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | unknown | yes | not provided | not provided | not provided | not provided | not provided | not provided | not provided |
From Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus, SCV001799931.1
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | not provided |
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | germline | yes | not provided | not provided | not provided | not provided | not provided | not provided | not provided |
From Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001807584.1
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | not provided |
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | germline | yes | not provided | not provided | not provided | not provided | not provided | not provided | not provided |
From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001967372.1
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | not provided |
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | germline | yes | not provided | not provided | not provided | not provided | not provided | not provided | not provided |
From Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden, SCV002009140.3
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | not provided | not provided | not provided | clinical testing | PubMed (1) |
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | germline | not provided | not provided | not provided | not provided | not provided | not provided | not provided | not provided |
From CeGaT Center for Human Genetics Tuebingen, SCV004151320.10
# | Ethnicity | Individuals | Chromosomes Tested | Family History | Method | Citations |
---|---|---|---|---|---|---|
1 | not provided | 2 | not provided | not provided | clinical testing | not provided |
Description
BARD1: BS1
# | Sample | Method | Observation | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences | |
1 | germline | yes | not provided | not provided | not provided | 2 | not provided | not provided | not provided |
Last Updated: Oct 20, 2024