NM_000059.4(BRCA2):c.4090A>G (p.Ile1364Val) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Mar 23, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000130224.10

Allele description [Variation Report for NM_000059.4(BRCA2):c.4090A>G (p.Ile1364Val)]

NM_000059.4(BRCA2):c.4090A>G (p.Ile1364Val)

Gene:

BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.4090A>G (p.Ile1364Val)

HGVS:

NC_000013.11:g.32338445A>G
NG_012772.3:g.27966A>G
NM_000059.4:c.4090A>GMANE SELECT
NP_000050.2:p.Ile1364Val
NP_000050.3:p.Ile1364Val
LRG_293t1:c.4090A>G
LRG_293:g.27966A>G
LRG_293p1:p.Ile1364Val
NC_000013.10:g.32912582A>G
NM_000059.3:c.4090A>G
p.I1364V

Protein change:

I1364V

Links:

dbSNP: rs56248502

NCBI 1000 Genomes Browser:

rs56248502

Molecular consequence:

NM_000059.4:c.4090A>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000185064	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jun 21, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23697973, 32894085 Citation Link,
SCV003848671	University of Washington Department of Laboratory Medicine, University of Washington	criteria provided, single submitter (Dines et al. (Genet Med. 2020))	Likely benign (Mar 23, 2023)	germline	curation	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000185064

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jun 21, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV003848671

University of Washington Department of Laboratory Medicine, University of Washington

criteria provided, single submitter

(Dines et al. (Genet Med. 2020))

Likely benign
(Mar 23, 2023)

germline

curation

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, curation

Citations

PubMed

BRCA1 and BRCA2 germline mutation spectrum in hereditary breast/ovarian cancer families from Maghrebian countries.

Cherbal F, Bakour R, Adane S, Boualga K.

Breast Dis. 2012;34(1):1-8. doi: 10.3233/BD-130348. Review.

PubMed [citation]

PMID:: 23697973

Contribution of BRCA1 and BRCA2 germline mutations to early onset breast cancer: a series from north of Morocco.

Bakkach J, Mansouri M, Derkaoui T, Loudiyi A, El Fahime E, Barakat A, Ghailani Nourouti N, Martinez De Villarreal J, Cortijo Bringas C, Bennani Mechita M.

BMC Cancer. 2020 Sep 7;20(1):859. doi: 10.1186/s12885-020-07352-9.

PubMed [citation]

PMID:: 32894085
PMCID:: PMC7487731

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000185064.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.I1364V variant (also known as c.4090A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 4090. The isoleucine at codon 1364 is replaced by valine, an amino acid with highly similar properties. This alteration has been identified in an individual diagnosed with breast cancer (Bakkach J et al. BMC Cancer, 2020 Sep;20:859). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. 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 University of Washington Department of Laboratory Medicine, University of Washington, SCV003848671.1

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

Description

Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).

#	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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