NM_000465.4(BARD1):c.79G>C (p.Glu27Gln) AND Familial cancer of breast

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 29, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000204805.16

Allele description [Variation Report for NM_000465.4(BARD1):c.79G>C (p.Glu27Gln)]

NM_000465.4(BARD1):c.79G>C (p.Glu27Gln)

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.79G>C (p.Glu27Gln)

Other names:

p.E27Q:GAA>CAA

HGVS:

NC_000002.12:g.214809491C>G
NG_012047.3:g.5221G>C
NM_000465.4:c.79G>CMANE SELECT
NM_001282543.2:c.79G>C
NM_001282545.2:c.79G>C
NM_001282548.2:c.79G>C
NM_001282549.2:c.79G>C
NP_000456.2:p.Glu27Gln
NP_001269472.1:p.Glu27Gln
NP_001269474.1:p.Glu27Gln
NP_001269477.1:p.Glu27Gln
NP_001269478.1:p.Glu27Gln
LRG_297t1:c.79G>C
LRG_297:g.5221G>C
LRG_297p1:p.Glu27Gln
NC_000002.11:g.215674215C>G
NG_012047.2:g.5214G>C
NM_000465.2:c.79G>C
NM_000465.3:c.79G>C
NR_104212.2:n.193G>C
NR_104215.2:n.193G>C
NR_104216.2:n.193G>C
p.E27Q

Protein change:

E27Q

Links:

dbSNP: rs587780037

NCBI 1000 Genomes Browser:

rs587780037

Molecular consequence:

NM_000465.4:c.79G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282543.2:c.79G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282545.2:c.79G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282548.2:c.79G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282549.2:c.79G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_104212.2:n.193G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.193G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104216.2:n.193G>C - 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
SCV000262423	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 28, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 36187937, 26350354, 28492532
SCV004214998	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 29, 2024)	unknown	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

SCV000262423

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 28, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004214998

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 29, 2024)

unknown

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

BRCA1-associated RING domain-1 (BARD1) loss and GBP1 expression enhance sensitivity to DNA damage in Ewing sarcoma.

Maurer LM, Daley JD, Mukherjee E, Venier RE, Julian CM, Bailey NG, Jacobs MF, Kumar-Sinha C, Raphael H, Periyapatna N, Weiss K, Janeway KA, Mody R, Lucas PC, McAllister-Lucas LM, Bailey KM.

Cancer Res Commun. 2022 Apr;2(4):220-232. doi: 10.1158/2767-9764.crc-21-0047. Epub 2022 Apr 20.

PubMed [citation]

PMID:: 36187937
PMCID:: PMC9524505

Functional Analysis of BARD1 Missense Variants in Homology-Directed Repair of DNA Double Strand Breaks.

Lee C, Banerjee T, Gillespie J, Ceravolo A, Parvinsmith MR, Starita LM, Fields S, Toland AE, Parvin JD.

Hum Mutat. 2015 Dec;36(12):1205-14. doi: 10.1002/humu.22902. Epub 2015 Sep 22.

PubMed [citation]

PMID:: 26350354
PMCID:: PMC6005381

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000262423.11

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 27 of the BARD1 protein (p.Glu27Gln). This variant is present in population databases (rs587780037, gnomAD 0.009%). This missense change has been observed in individual(s) with B-cell acute lymphoblastic leukemia (PMID: 36187937). ClinVar contains an entry for this variant (Variation ID: 127748). 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 tolerated. Experimental studies have shown that this missense change does not substantially affect BARD1 function (PMID: 26350354). 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

From Baylor Genetics, SCV004214998.2

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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