NM_000465.4(BARD1):c.2324_2325del (p.Leu775fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 21, 2023
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:: RCV000130512.13

Allele description [Variation Report for NM_000465.4(BARD1):c.2324_2325del (p.Leu775fs)]

NM_000465.4(BARD1):c.2324_2325del (p.Leu775fs)

Gene:

BARD1:BRCA1 associated RING domain 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_000465.4(BARD1):c.2324_2325del (p.Leu775fs)

HGVS:

NC_000002.12:g.214728685_214728686del
NG_012047.3:g.86026_86027del
NM_000465.4:c.2324_2325delMANE SELECT
NM_001282543.2:c.2267_2268del
NM_001282545.2:c.971_972del
NM_001282548.2:c.914_915del
NM_001282549.2:c.785_786del
NP_000456.2:p.Leu775fs
NP_001269472.1:p.Leu756fs
NP_001269474.1:p.Leu324fs
NP_001269477.1:p.Leu305fs
NP_001269478.1:p.Leu262fs
LRG_297t1:c.2324_2325del
LRG_297:g.86026_86027del
LRG_297p1:p.Leu775fs
NC_000002.11:g.215593409_215593410del
NG_012047.2:g.86019_86020del
NM_000465.2:c.2324_2325del
NM_000465.2:c.2324_2325delTT
NM_000465.3:c.2324_2325del
NM_000465.3:c.2324_2325delTT
NR_104212.2:n.2289_2290del
NR_104215.2:n.2232_2233del
NR_104216.2:n.1488_1489del
p.L775Rfs*19

Protein change:

L262fs

Links:

dbSNP: rs587782046

NCBI 1000 Genomes Browser:

rs587782046

Molecular consequence:

NM_000465.4:c.2324_2325del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282543.2:c.2267_2268del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282545.2:c.971_972del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282548.2:c.914_915del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282549.2:c.785_786del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_104212.2:n.2289_2290del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.2232_2233del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104216.2:n.1488_1489del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000185381	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Sep 21, 2023)	germline	clinical testing	Citation Link,
SCV000682772	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 23, 2019)	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

SCV000185381

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Sep 21, 2023)

germline

clinical testing

Citation Link,

SCV000682772

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 23, 2019)

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Ambry Genetics, SCV000185381.8

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

Description

The c.2324_2325delTT variant, located in coding exon 11 of the BARD1 gene, results from a deletion of two nucleotides at nucleotide positions 2324 to 2325. This alteration changes the last three residues of the BARD1 protein and results in the elongation of the protein by 15 amino acids before introducing an alternate stop codon (p.L775Rfs*19). This alteration occurs at the 3' terminus of theBARD1 gene, is not expected to trigger nonsense-mediated mRNAdecay and results in the elongation of the protein by 15 amino acids. This frameshift impacts the last 3amino acids of the native protein. The exact functional effect of the altered amino acids is unknown. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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 Color Diagnostics, LLC DBA Color Health, SCV000682772.3

#	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	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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