Submissions for variant NM_000465.4(BARD1):c.1203T>C (p.Ser401=)

gnomAD frequency: 0.00014  dbSNP: rs370553043

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000164204	SCV000214825	likely benign	Hereditary cancer-predisposing syndrome	2015-06-10	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Invitae	RCV000987017	SCV000284900	likely benign	Familial cancer of breast	2024-01-25	criteria provided, single submitter	clinical testing
GeneDx	RCV000679330	SCV000512242	likely benign	not provided	2021-10-18	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 19197335, 20077502, 26738429)
Color Diagnostics, LLC DBA Color Health	RCV000164204	SCV000537484	likely benign	Hereditary cancer-predisposing syndrome	2015-07-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000679330	SCV000806100	likely benign	not provided	2017-07-27	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000679330	SCV000887581	benign	not provided	2022-10-03	criteria provided, single submitter	clinical testing
Mendelics	RCV000987017	SCV001136191	benign	Familial cancer of breast	2019-05-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000444966	SCV001774460	likely benign	not specified	2021-07-19	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000164204	SCV002526993	likely benign	Hereditary cancer-predisposing syndrome	2021-03-21	criteria provided, single submitter	curation
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354918	SCV001549646	likely benign	Lung cancer		no assertion criteria provided	clinical testing	The BARD1 c.1203T>C variant was identified in 2 of 584 proband chromosomes (frequency: 0.003) from individuals or families with breast and ovarian cancer and was not identified in 490 control chromosomes from healthy individuals (De Brakeleer 2010, Guenard 2009). The variant was also identified in the following databases: dbSNP (ID: rs370553043) as “With Likely benign allele”, ClinVar (5x, as likely benign, by Ambry genetics, Invitae, GeneDx, Color Genomics, Quest Diagnostics), Clinvitae (3x, as likely benign, by ClinVar and Invitae) and Zhejiang Colon Cancer Database (3x). The variant was not identified in Cosmic and MutDB databases. The variant was identified in control databases in 19 of 276710 chromosomes at a frequency of 0.00007 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 5 of 24030 chromosomes (freq: 0.0002), Latino in 1 of 34380 chromosomes (freq: 0.00003), European Non-Finnish in 12 of 126298 chromosomes (freq: 0.000095), and South Asian in 1 of 30778 chromosomes (freq: 0.000032); While the variant was not observed in the Other, Ashkenazi Jewish, East Asian and Finnish populations. The c.1203T>C variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, 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.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001355262	SCV001550092	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The BARD1 c.1203T>C variant was identified in 2 of 584 proband chromosomes (frequency: 0.003) from individuals or families with breast and ovarian cancer and was not identified in 490 control chromosomes from healthy individuals (De Brakeleer 2010, Guenard 2009). The variant was also identified in the following databases: dbSNP (ID: rs370553043) as “With Likely benign allele”, ClinVar (5x, as likely benign, by Ambry genetics, Invitae, GeneDx, Color Genomics, Quest Diagnostics), Clinvitae (3x, as likely benign, by ClinVar and Invitae) and Zhejiang Colon Cancer Database (3x). The variant was not identified in Cosmic and MutDB databases. The variant was identified in control databases in 19 of 276710 chromosomes at a frequency of 0.00007 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 5 of 24030 chromosomes (freq: 0.0002), Latino in 1 of 34380 chromosomes (freq: 0.00003), European Non-Finnish in 12 of 126298 chromosomes (freq: 0.000095), and South Asian in 1 of 30778 chromosomes (freq: 0.000032); While the variant was not observed in the Other, Ashkenazi Jewish, East Asian and Finnish populations. The c.1203T>C variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, 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.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001358102	SCV001553753	likely benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The BARD1 c.1203T>C variant was identified in 2 of 584 proband chromosomes (frequency: 0.003) from individuals or families with breast and ovarian cancer and was not identified in 490 control chromosomes from healthy individuals (De Brakeleer 2010, Guenard 2009). The variant was also identified in the following databases: dbSNP (ID: rs370553043) as “With Likely benign allele”, ClinVar (5x, as likely benign, by Ambry genetics, Invitae, GeneDx, Color Genomics, Quest Diagnostics), Clinvitae (3x, as likely benign, by ClinVar and Invitae) and Zhejiang Colon Cancer Database (3x). The variant was not identified in Cosmic and MutDB databases. The variant was identified in control databases in 19 of 276710 chromosomes at a frequency of 0.00007 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 5 of 24030 chromosomes (freq: 0.0002), Latino in 1 of 34380 chromosomes (freq: 0.00003), European Non-Finnish in 12 of 126298 chromosomes (freq: 0.000095), and South Asian in 1 of 30778 chromosomes (freq: 0.000032); While the variant was not observed in the Other, Ashkenazi Jewish, East Asian and Finnish populations. The c.1203T>C variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, 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.