Submissions for variant NM_000465.4(BARD1):c.2105T>C (p.Ile702Thr)

dbSNP: rs752114855

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000774621	SCV000908452	uncertain significance	Hereditary cancer-predisposing syndrome	2019-06-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001248631	SCV001422130	uncertain significance	Familial cancer of breast	2023-05-02	criteria provided, single submitter	clinical testing	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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 629851). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. This variant is present in population databases (rs752114855, gnomAD 0.003%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 702 of the BARD1 protein (p.Ile702Thr).
Ambry Genetics	RCV000774621	SCV005098875	likely benign	Hereditary cancer-predisposing syndrome	2024-03-28	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx	RCV004777863	SCV005390234	uncertain significance	not provided	2024-04-23	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 17550235)
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV004777863	SCV005625653	uncertain significance	not provided	2024-10-09	criteria provided, single submitter	clinical testing	The BARD1 c.2105T>C (p.Ile702Thr) variant has not been reported in individuals with BARD1-related conditions in the published literature. The frequency of this variant in the general population, 0.000004 (1/251296 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant.