NM_000465.4(BARD1):c.1289C>T (p.Thr430Ile) AND Familial cancer of breast

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 4, 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:: RCV001054243.9

Allele description [Variation Report for NM_000465.4(BARD1):c.1289C>T (p.Thr430Ile)]

NM_000465.4(BARD1):c.1289C>T (p.Thr430Ile)

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.1289C>T (p.Thr430Ile)

HGVS:

NC_000002.12:g.214780585G>A
NG_012047.3:g.34127C>T
NM_000465.4:c.1289C>TMANE SELECT
NM_001282543.2:c.1232C>T
NM_001282545.2:c.215+16476C>T
NM_001282548.2:c.159-28030C>T
NM_001282549.2:c.364+11712C>T
NP_000456.2:p.Thr430Ile
NP_001269472.1:p.Thr411Ile
LRG_297t1:c.1289C>T
LRG_297:g.34127C>T
LRG_297p1:p.Thr430Ile
NC_000002.11:g.215645309G>A
NG_012047.2:g.34120C>T
NM_000465.2:c.1289C>T
NM_000465.3:c.1289C>T
NR_104212.2:n.1254C>T
NR_104215.2:n.1197C>T

Protein change:

T411I

Links:

dbSNP: rs587780015

NCBI 1000 Genomes Browser:

rs587780015

Molecular consequence:

NM_001282545.2:c.215+16476C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001282548.2:c.159-28030C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001282549.2:c.364+11712C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000465.4:c.1289C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282543.2:c.1232C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_104212.2:n.1254C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.1197C>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

Recent activity

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Homo sapiens hypothetical protein BC000993 (LOC130026), mRNA
Homo sapiens hypothetical protein BC000993 (LOC130026), mRNA
gi|19924000|ref|NM_138468.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001218547	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 4, 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

SCV001218547

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 4, 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, SCV001218547.5

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

Description

ClinVar contains an entry for this variant (Variation ID: 495873). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 430 of the BARD1 protein (p.Thr430Ile). 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.

#	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

ClinVar

Relating variation to medicine