NM_000059.4(BRCA2):c.3916G>A (p.Val1306Ile) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Jan 26, 2024
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:: RCV000203660.25

Allele description [Variation Report for NM_000059.4(BRCA2):c.3916G>A (p.Val1306Ile)]

NM_000059.4(BRCA2):c.3916G>A (p.Val1306Ile)

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.3916G>A (p.Val1306Ile)

Other names:

V1360I; V1360L; p.V1306I:GTT>ATT

HGVS:

NC_000013.11:g.32338271G>A
NG_012772.3:g.27792G>A
NM_000059.4:c.3916G>AMANE SELECT
NP_000050.2:p.Val1306Ile
NP_000050.3:p.Val1306Ile
LRG_293t1:c.3916G>A
LRG_293:g.27792G>A
LRG_293p1:p.Val1306Ile
NC_000013.10:g.32912408G>A
NM_000059.3:c.3916G>A
U43746.1:n.4144G>A
p.V1306I

Nucleotide change:

4144G>A

Protein change:

V1306I

Links:

dbSNP: rs80358636

NCBI 1000 Genomes Browser:

rs80358636

Molecular consequence:

NM_000059.4:c.3916G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary breast ovarian cancer syndrome
Synonyms:: Hereditary breast and ovarian cancer syndrome; Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000072322	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Jan 26, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000257609	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	criteria provided, single submitter (DGD Variant Analysis Guidelines)	Uncertain significance (Apr 12, 2015)	unknown	clinical testing	DGD_Variant_Analysis_Guidelines.docx, Citation Link,
SCV000890966	St. Jude Molecular Pathology, St. Jude Children's Research Hospital	criteria provided, single submitter (St. Jude Assertion Criteria 2020)	Likely benign (Aug 26, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000072322

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Jan 26, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000257609

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

criteria provided, single submitter

(DGD Variant Analysis Guidelines)

Uncertain significance
(Apr 12, 2015)

unknown

clinical testing

DGD_Variant_Analysis_Guidelines.docx,

Citation Link,

SCV000890966

St. Jude Molecular Pathology, St. Jude Children's Research Hospital

criteria provided, single submitter

(St. Jude Assertion Criteria 2020)

Likely benign
(Aug 26, 2021)

germline

clinical testing

Citation Link

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000072322.13

#	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

From Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia, SCV000257609.2

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From St. Jude Molecular Pathology, St. Jude Children's Research Hospital, SCV000890966.3

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

Description

The BRCA2 c.3916G>A (p.Val1306Ile) missense change has a maximum subpopulation frequency of 0.0041% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/13-32912408-G-A). Six of seven in silico tools predict a benign effect of this variant on protein function (BP4), but to our knowledge these predictions have not been confirmed by functional assays. This variant has been reported in two women older than 70 years of age who have never had cancer (BS2_supporting; https://whi.color.com/variant/13-32907401-G-C). It has also been reported in an individual with breast cancer (PMID: 20104584). In summary, this variant meets criteria to be classified as likely benign based on the ACMG/AMP criteria: BS2_supporting, BP4.

#	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: Oct 20, 2024

ClinVar

Relating variation to medicine