NM_000059.4(BRCA2):c.9857T>A (p.Ile3286Asn) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 2, 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:: RCV000077053.5

Allele description [Variation Report for NM_000059.4(BRCA2):c.9857T>A (p.Ile3286Asn)]

NM_000059.4(BRCA2):c.9857T>A (p.Ile3286Asn)

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.9857T>A (p.Ile3286Asn)

HGVS:

NC_000013.11:g.32398370T>A
NG_012772.3:g.87891T>A
NM_000059.4:c.9857T>AMANE SELECT
NP_000050.2:p.Ile3286Asn
NP_000050.3:p.Ile3286Asn
LRG_293t1:c.9857T>A
LRG_293:g.87891T>A
LRG_293p1:p.Ile3286Asn
NC_000013.10:g.32972507T>A
NM_000059.3:c.9857T>A
p.I3286N

Nucleotide change:

10085T>A

Protein change:

I3286N

Links:

dbSNP: rs398122624

NCBI 1000 Genomes Browser:

rs398122624

Molecular consequence:

NM_000059.4:c.9857T>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Breast-ovarian cancer, familial, susceptibility to, 2 (BROVCA2)
Synonyms:: Breast-ovarian cancer, familial 2
Identifiers:: MONDO: MONDO:0012933; MedGen: C2675520; Orphanet: 145; OMIM: 612555

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000108850	Sharing Clinical Reports Project (SCRP)	no assertion criteria provided	Uncertain significance (Oct 28, 2011)	germline	clinical testing
SCV004837733	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Nov 2, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 28993434, 32444794, 33471991, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000108850

Sharing Clinical Reports Project (SCRP)

no assertion criteria provided

Uncertain significance
(Oct 28, 2011)

germline

clinical testing

SCV004837733

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Nov 2, 2023)

germline

clinical testing

PubMed (4)
[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	not provided	1	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Inherited mutations in BRCA1 and BRCA2 in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia.

Wen WX, Allen J, Lai KN, Mariapun S, Hasan SN, Ng PS, Lee DS, Lee SY, Yoon SY, Lim J, Lau SY, Decker B, Pooley K, Dorling L, Luccarini C, Baynes C, Conroy DM, Harrington P, Simard J, Yip CH, Mohd Taib NA, Ho WK, et al.

J Med Genet. 2018 Feb;55(2):97-103. doi: 10.1136/jmedgenet-2017-104947. Epub 2017 Oct 9.

PubMed [citation]

PMID:: 28993434
PMCID:: PMC5800345

High-throughput functional evaluation of BRCA2 variants of unknown significance.

Ikegami M, Kohsaka S, Ueno T, Momozawa Y, Inoue S, Tamura K, Shimomura A, Hosoya N, Kobayashi H, Tanaka S, Mano H.

Nat Commun. 2020 May 22;11(1):2573. doi: 10.1038/s41467-020-16141-8.

PubMed [citation]

PMID:: 32444794
PMCID:: PMC7244490

See all PubMed Citations (4)

Details of each submission

From Sharing Clinical Reports Project (SCRP), SCV000108850.2

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

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

From All of Us Research Program, National Institutes of Health, SCV004837733.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (4)

Description

This missense variant replaces isoleucine with asparagine at codon 3286 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). A functional study has shown that this variant does not impact sensitivity to PARP inhibitors (PMID: 32444794). This variant has been reported in at least two individuals affected with breast cancer (PMID: 28993434, 33471991; Leiden Open Variation Database DB-ID BRCA2_008801). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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	108544	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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