Total submissions: 25
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000212135 | SCV000149525 | pathogenic | not provided | 2022-04-16 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate a damaging effect: significantly reduced homology-directed repair and may result in abnormal splicing (Ratajska 2015, Adamovich 2019); Case control studies suggest this variant is associated with breast cancer (Suszynska 2019); Observed in multiple individuals with personal and/or family history of breast, ovarian, colorectal, or endometrial cancer (Ratajska 2012, Blazer 2015, De Brakeleer 2015, Klonowska 2015, Ramus 2015, Maxwell 2016, Ring 2016, Weber-Lassalle 2019); This variant is associated with the following publications: (PMID: 25330149, 26075229, 26083025, 27443514, 31371347, 26681312, 31589614, 29922827, 28888541, 32726901, 21344236, 26010302, 25994375, 25980754, 26539620, 26738429, 26315354, 28030839, 27153395, 26329992, 30925164, 31036035, 28008555, 30675285, 31173646, 31142030, 29506128, 30947698, 31159747, 29625052, 26689913) |
Ambry Genetics | RCV000115616 | SCV000215789 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-11-15 | criteria provided, single submitter | clinical testing | The p.Q564* pathogenic mutation (also known as c.1690C>T), located in coding exon 8 of the BARD1 gene, results from a C to T substitution at nucleotide position 1690. This changes the amino acid from a glutamine to a stop codon within coding exon 8. This alteration has been reported in numerous patients diagnosed with breast and/or ovarian cancer (Ratajska M et al. Breast Cancer Res. Treat. 2012 Jan;131:89-97; Cybulski C et al. Clin. Genet. 2015 Oct;88:366-70; Klonowska K et al. Sci. Rep. 2015 May;5:10424; Ramus SJ et al. J Natl Cancer Inst. 2015 Nov;107:; Weber-Lassalle N et al. Breast Cancer Res. 2019 04;21:55; Shahi RB et al. BMC Cancer. 2019 Apr;19:313). Additionally, this alteration has been identified in a patient with triple-negative breast cancer (De Brakeleer S et al. Clin. Genet. 2016 Mar;89(3):336-40) and a male breast cancer patient (Pritzlaff M et al. Breast Cancer Res. Treat. 2017 Feb;161:575-586). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Labcorp Genetics |
RCV000205536 | SCV000260996 | pathogenic | Familial cancer of breast | 2024-01-26 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln564*) in the BARD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BARD1 are known to be pathogenic (PMID: 20077502, 21344236). This variant is present in population databases (rs587780021, gnomAD 0.005%). This premature translational stop signal has been observed in individual(s) with breast and ovarian cancer (PMID: 21344236, 25994375, 26010302, 26315354, 26329992, 26681312, 27443514). ClinVar contains an entry for this variant (Variation ID: 127720). For these reasons, this variant has been classified as Pathogenic. |
Color Diagnostics, |
RCV000115616 | SCV000682724 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-11-06 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 8 of the BARD1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in over 15 individuals affected with breast or ovarian cancer (PMID: 25994375, 26010302, 26315354, 26329992, 26681312, 28008555, 29625052, 30947698, 31036035, 32679805, 37239058, 37563628) and one individual affected with endometrial cancer (PMID: 27443514). In a large breast cancer case-control meta analysis, this variant has been observed in 17/60449 cases and 6/53455 controls (PMID: 33471991; Leiden Open Variation Database DB-ID BARD1_000187). This variant has been identified in 7/282686 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BARD1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588742 | SCV000696755 | pathogenic | Hereditary breast ovarian cancer syndrome | 2019-12-10 | criteria provided, single submitter | clinical testing | Variant summary: BARD1 c.1690C>T (p.Gln564X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. 5/5 computational tools predict no significant impact on normal splicing. However, Ratajska_2015 report that this variant may have an impact on splicing alteration. The variant allele was found at a frequency of 2.4e-05 in 252390 control chromosomes (gnomAD). c.1690C>T has been reported in the literature in multiple individuals affected with breast and/or ovarian cancer patients (e.g. Cybulski_2014, Weber-Lassalle_2019). These data indicate that the variant is very likely to be associated with disease. Nine other ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Gene |
RCV000212135 | SCV000821706 | pathogenic | not provided | 2020-01-01 | criteria provided, single submitter | clinical testing | This variant results in the creation of a premature translational stop signal at codon 564 of the BARD1 protein (p.Gln564*). It is expected to result in absent or disrupted protein product. This variant has been described in the literature in patients with a strong family or personal history of breast and/or ovarian cancer (PMID: 21344236, PMID: 25994375, PMID: 26010302).The mutation database ClinVar contains an entry for this variant (Variation ID: 127720). |
Mendelics | RCV000205536 | SCV000837958 | pathogenic | Familial cancer of breast | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000212135 | SCV000888798 | pathogenic | not provided | 2024-10-08 | criteria provided, single submitter | clinical testing | The BARD1 c.1690C>T (p.Gln564*) variant causes the premature termination of BARD1 protein synthesis. This variant has been reported in the published literature in patients with breast/ovarian cancer (PMIDs: 21344236 (2012), 26315354 (2015), 26329992 (2015), 26010302 (2016), 27153395 (2016), 30947698 (2019), 31036035 (2019), 37239058 (2023), and 37563628 (2023)), male breast cancer (PMID: 28008555 (2017)), endometrial cancer (PMID: 27443514 (2016)), and in a cohort of individuals tested for Lynch syndrome (PMID: 25980754 (2015)). The frequency of this variant in the general population, 0.000054 (7/129052 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic. |
Fulgent Genetics, |
RCV000205536 | SCV000893572 | pathogenic | Familial cancer of breast | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000212135 | SCV001247082 | pathogenic | not provided | 2024-04-01 | criteria provided, single submitter | clinical testing | BARD1: PVS1, PS4 |
Institute of Medical Genetics and Applied Genomics, |
RCV000212135 | SCV001447809 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Institute for Clinical Genetics, |
RCV000212135 | SCV002009151 | pathogenic | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000115616 | SCV002527045 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-09-04 | criteria provided, single submitter | curation | |
MGZ Medical Genetics Center | RCV000205536 | SCV002579961 | pathogenic | Familial cancer of breast | 2022-07-20 | criteria provided, single submitter | clinical testing | |
Centre for Mendelian Genomics, |
RCV000205536 | SCV002762790 | pathogenic | Familial cancer of breast | 2022-12-09 | criteria provided, single submitter | research | PVS1, PS3, PS4_STR |
Myriad Genetics, |
RCV000205536 | SCV004044108 | pathogenic | Familial cancer of breast | 2023-05-23 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
Prevention |
RCV003415888 | SCV004108471 | pathogenic | BARD1-related disorder | 2023-07-12 | criteria provided, single submitter | clinical testing | The BARD1 c.1690C>T variant is predicted to result in premature protein termination (p.Gln564*). This variant has been reported in many individuals with breast and/or ovarian cancer (Ratajska et al 2012. PubMed ID: 21344236; Yurgelun MB et al 2015. PubMed ID: 25980754; Klonowska K et al 2015. PubMed ID: 25994375; Ratajska M et al 2015. PubMed ID: 26329992; Lu C et al 2015. PubMed ID: 26689913; Maxwell KN et al 2016. PubMed ID: 27153395; Lilyquist J et al 2017. PubMed ID: 28888541; Lowery MA et al 2018. PubMed ID: 29506128; Huang KL et al 2018. PubMed ID: 29625052; Shahi RB et al 2019. PubMed ID: 30947698; Weber-Lassalle N et al 2019. PubMed ID: 31036035; Tsaousis GN et al 2019. PubMed ID: 31159747). This variant is reported in 0.0054% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-215610566-G-A) and is interpreted as pathogenic (15) and uncertain significance (1) in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/127720/). Nonsense variants in BARD1 are expected to be pathogenic. This variant is interpreted as pathogenic. |
Baylor Genetics | RCV000205536 | SCV004217284 | pathogenic | Familial cancer of breast | 2023-11-27 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000212135 | SCV004238505 | pathogenic | not provided | 2021-01-21 | criteria provided, single submitter | clinical testing | |
Center for Genomic Medicine, |
RCV000212135 | SCV004243118 | pathogenic | not provided | 2024-02-06 | criteria provided, single submitter | clinical testing | |
Clinical Genetics Laboratory, |
RCV000212135 | SCV005199666 | pathogenic | not provided | 2024-02-02 | criteria provided, single submitter | clinical testing | |
Lab. |
RCV000678225 | SCV000804244 | pathogenic | Triple-Negative Breast Cancer Finding | 2015-02-01 | no assertion criteria provided | clinical testing | |
CZECANCA consortium | RCV001270956 | SCV001451760 | pathogenic | Breast and/or ovarian cancer | 2019-06-11 | no assertion criteria provided | clinical testing | |
BRCAlab, |
RCV000205536 | SCV002589054 | pathogenic | Familial cancer of breast | 2022-08-26 | no assertion criteria provided | clinical testing | |
CZECANCA consortium | RCV003128144 | SCV003804342 | pathogenic | Endometrial carcinoma | 2023-02-21 | no assertion criteria provided | clinical testing |