Submissions for variant NM_000465.4(BARD1):c.1569-13C>G

gnomAD frequency: 0.00002  dbSNP: rs587780018

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000115613	SCV000149522	uncertain significance	not provided	2024-03-05	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; Observed in individuals with breast cancer or Lynch-related cancers and/or polyps (PMID: 25980754, 35264596); This variant is associated with the following publications: (PMID: 35264596, 25980754)
Color Diagnostics, LLC DBA Color Health	RCV000580058	SCV000682709	uncertain significance	Hereditary cancer-predisposing syndrome	2023-11-01	criteria provided, single submitter	clinical testing	This variant causes a C to G nucleotide substitution at the -13 position of intron 6 of the BARD1 gene. Splice site prediction tools predict that this variant may impact RNA splicing, however, this prediction has not been confirmed in published RNA studies. This variant has been reported in an individual affected with breast cancer (PMID: 35264596) and an individual affected with Lynch syndrome-associated cancer and/or polyps (PMID: 25980754). This variant has been identified in 5/251050 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Mendelics	RCV000708905	SCV000837961	uncertain significance	Familial cancer of breast	2018-07-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000708905	SCV002131425	uncertain significance	Familial cancer of breast	2024-12-22	criteria provided, single submitter	clinical testing	This sequence change falls in intron 6 of the BARD1 gene. It does not directly change the encoded amino acid sequence of the BARD1 protein. This variant is present in population databases (rs587780018, gnomAD 0.004%). This variant has been observed in individual(s) with breast cancer (PMID: 35264596, 35980532). ClinVar contains an entry for this variant (Variation ID: 127717). Studies have shown that this variant is associated with altered splicing resulting in multiple RNA products (internal data). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV003320564	SCV004024850	uncertain significance	not specified	2025-03-04	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000708905	SCV004043173	likely pathogenic	Familial cancer of breast	2023-09-29	criteria provided, single submitter	clinical testing	This variant is considered likely pathogenic. This variant is strongly associated with more severe personal and family histories of cancer, typical for individuals with pathogenic variants in this gene [PMID: 25085752].
Baylor Genetics	RCV000708905	SCV004214954	uncertain significance	Familial cancer of breast	2024-02-19	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000580058	SCV004849335	uncertain significance	Hereditary cancer-predisposing syndrome	2014-12-11	criteria provided, single submitter	clinical testing	The c.1569-13C>G intronic alteration consists of a C to G substitution 13 nucleotides before coding exon 7 in the BARD1 gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.