NM_000465.4(BARD1):c.57G>C (p.Glu19Asp) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Nov 11, 2022
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:: RCV001549408.7

Allele description [Variation Report for NM_000465.4(BARD1):c.57G>C (p.Glu19Asp)]

NM_000465.4(BARD1):c.57G>C (p.Glu19Asp)

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.57G>C (p.Glu19Asp)

HGVS:

NC_000002.12:g.214809513C>G
NG_012047.3:g.5199G>C
NM_000465.4:c.57G>CMANE SELECT
NM_001282543.2:c.57G>C
NM_001282545.2:c.57G>C
NM_001282548.2:c.57G>C
NM_001282549.2:c.57G>C
NP_000456.2:p.Glu19Asp
NP_001269472.1:p.Glu19Asp
NP_001269474.1:p.Glu19Asp
NP_001269477.1:p.Glu19Asp
NP_001269478.1:p.Glu19Asp
LRG_297t1:c.57G>C
LRG_297:g.5199G>C
LRG_297p1:p.Glu19Asp
NC_000002.11:g.215674237C>G
NG_012047.2:g.5192G>C
NM_000465.2:c.57G>C
NM_000465.3:c.57G>C
NR_104212.2:n.171G>C
NR_104215.2:n.171G>C
NR_104216.2:n.171G>C

Protein change:

E19D

Links:

dbSNP: rs730881406

NCBI 1000 Genomes Browser:

rs730881406

Molecular consequence:

NM_000465.4:c.57G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282543.2:c.57G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282545.2:c.57G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282548.2:c.57G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282549.2:c.57G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_104212.2:n.171G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.171G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104216.2:n.171G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001769553	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Nov 11, 2022)	germline	clinical testing	Citation Link,
SCV004222404	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Oct 21, 2022)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 33471991, 26315354, 26467025
SCV005188262	Breakthrough Genomics, Breakthrough Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	germline	not provided	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001769553

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Nov 11, 2022)

germline

clinical testing

Citation Link,

SCV004222404

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Oct 21, 2022)

unknown

clinical testing

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

SCV005188262

Breakthrough Genomics, Breakthrough Genomics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance

germline

not provided

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing, not provided

Citations

PubMed

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Breast Cancer Association Consortium., Dorling L, Carvalho S, Allen J, González-Neira A, Luccarini C, Wahlström C, Pooley KA, Parsons MT, Fortuno C, Wang Q, Bolla MK, Dennis J, Keeman R, Alonso MR, Álvarez N, Herraez B, Fernandez V, Núñez-Torres R, Osorio A, Valcich J, Li M, et al.

N Engl J Med. 2021 Feb 4;384(5):428-439. doi: 10.1056/NEJMoa1913948. Epub 2021 Jan 20.

PubMed [citation]

PMID:: 33471991
PMCID:: PMC7611105

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

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV001769553.3

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with ovarian cancer (Ramus et al., 2015); This variant is associated with the following publications: (PMID: 26787654, 26315354, 33471991)

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004222404.1

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

Description

The frequency of this variant in the general population, 0.0000092 (2/218120 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in an individual with ovarian cancer (PMID: 26315354 (2015)). In a large-scale breast cancer association study, the variant was observed in an individual with breast cancer (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/BARD1)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.

#	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

From Breakthrough Genomics, Breakthrough Genomics, SCV005188262.1

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

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

Last Updated: Sep 29, 2024

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