NM_000465.4(BARD1):c.977A>G (p.Asn326Ser) AND Familial cancer of breast

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 13, 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:: RCV000456378.10

Allele description [Variation Report for NM_000465.4(BARD1):c.977A>G (p.Asn326Ser)]

NM_000465.4(BARD1):c.977A>G (p.Asn326Ser)

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.977A>G (p.Asn326Ser)

HGVS:

NC_000002.12:g.214780897T>C
NG_012047.3:g.33815A>G
NM_000465.4:c.977A>GMANE SELECT
NM_001282543.2:c.920A>G
NM_001282545.2:c.215+16164A>G
NM_001282548.2:c.159-28342A>G
NM_001282549.2:c.364+11400A>G
NP_000456.2:p.Asn326Ser
NP_001269472.1:p.Asn307Ser
LRG_297t1:c.977A>G
LRG_297:g.33815A>G
LRG_297p1:p.Asn326Ser
NC_000002.11:g.215645621T>C
NG_012047.2:g.33808A>G
NM_000465.2:c.977A>G
NM_000465.3:c.977A>G
NR_104212.2:n.942A>G
NR_104215.2:n.885A>G

Protein change:

N307S

Links:

dbSNP: rs779960429

NCBI 1000 Genomes Browser:

rs779960429

Molecular consequence:

NM_001282545.2:c.215+16164A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001282548.2:c.159-28342A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001282549.2:c.364+11400A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000465.4:c.977A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282543.2:c.920A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_104212.2:n.942A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.885A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial
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
SCV000545611	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 13, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26315354, 30925164, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000545611

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 13, 2023)

germline

clinical testing

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

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

Germline Mutations in the BRIP1, BARD1, PALB2, and NBN Genes in Women With Ovarian Cancer.

Ramus SJ, Song H, Dicks E, Tyrer JP, Rosenthal AN, Intermaggio MP, Fraser L, Gentry-Maharaj A, Hayward J, Philpott S, Anderson C, Edlund CK, Conti D, Harrington P, Barrowdale D, Bowtell DD, Alsop K, Mitchell G; AOCS Study Group., Cicek MS, Cunningham JM, Fridley BL, et al.

J Natl Cancer Inst. 2015 Aug 27;107(11). doi:pii: djv214. 10.1093/jnci/djv214. Print 2015 Nov.

PubMed [citation]

PMID:: 26315354
PMCID:: PMC4643629

Functional analysis of BARD1 missense variants in homology-directed repair and damage sensitivity.

Adamovich AI, Banerjee T, Wingo M, Duncan K, Ning J, Martins Rodrigues F, Huang KL, Lee C, Chen F, Ding L, Parvin JD.

PLoS Genet. 2019 Mar;15(3):e1008049. doi: 10.1371/journal.pgen.1008049.

PubMed [citation]

PMID:: 30925164
PMCID:: PMC6457558

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000545611.9

#	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 asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 326 of the BARD1 protein (p.Asn326Ser). This variant is present in population databases (rs779960429, gnomAD 0.0009%). This missense change has been observed in individual(s) with ovarian cancer (PMID: 26315354). ClinVar contains an entry for this variant (Variation ID: 406763). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change does not substantially affect BARD1 function (PMID: 30925164). 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: Jul 15, 2024

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