NM_000465.4(BARD1):c.2279C>T (p.Ser760Leu) AND Familial cancer of breast

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 24, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000793827.10

Allele description [Variation Report for NM_000465.4(BARD1):c.2279C>T (p.Ser760Leu)]

NM_000465.4(BARD1):c.2279C>T (p.Ser760Leu)

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.2279C>T (p.Ser760Leu)

HGVS:

NC_000002.12:g.214728731G>A
NG_012047.3:g.85981C>T
NM_000465.4:c.2279C>TMANE SELECT
NM_001282543.2:c.2222C>T
NM_001282545.2:c.926C>T
NM_001282548.2:c.869C>T
NM_001282549.2:c.740C>T
NP_000456.2:p.Ser760Leu
NP_001269472.1:p.Ser741Leu
NP_001269474.1:p.Ser309Leu
NP_001269477.1:p.Ser290Leu
NP_001269478.1:p.Ser247Leu
LRG_297t1:c.2279C>T
LRG_297:g.85981C>T
LRG_297p1:p.Ser760Leu
NC_000002.11:g.215593455G>A
NG_012047.2:g.85974C>T
NM_000465.2:c.2279C>T
NM_000465.3:c.2279C>T
NR_104212.2:n.2244C>T
NR_104215.2:n.2187C>T
NR_104216.2:n.1443C>T

Protein change:

S247L

Links:

dbSNP: rs730881425

NCBI 1000 Genomes Browser:

rs730881425

Molecular consequence:

NM_000465.4:c.2279C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282543.2:c.2222C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282545.2:c.926C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282548.2:c.869C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282549.2:c.740C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_104212.2:n.2244C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.2187C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104216.2:n.1443C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial; Hereditary breast cancer
Identifiers:: MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000933203	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 24, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000933203

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 24, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000933203.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 760 of the BARD1 protein (p.Ser760Leu). This variant is present in population databases (rs730881425, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 479129). 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. 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.

#	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

Last Updated: Sep 29, 2024

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