NM_000059.4(BRCA2):c.4046T>C (p.Ile1349Thr) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:: Benign (3 submissions)
Last evaluated:: Aug 10, 2015
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV000113266.12

Allele description [Variation Report for NM_000059.4(BRCA2):c.4046T>C (p.Ile1349Thr)]

NM_000059.4(BRCA2):c.4046T>C (p.Ile1349Thr)

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.4046T>C (p.Ile1349Thr)

Other names:

p.I1349T:ATT>ACT; 4274T>C

HGVS:

NC_000013.11:g.32338401T>C
NG_012772.3:g.27922T>C
NM_000059.4:c.4046T>CMANE SELECT
NP_000050.2:p.Ile1349Thr
NP_000050.3:p.Ile1349Thr
LRG_293t1:c.4046T>C
LRG_293:g.27922T>C
LRG_293p1:p.Ile1349Thr
NC_000013.10:g.32912538T>C
NM_000059.3:c.4046T>C
U43746.1:n.4274T>C
p.I1349T

Protein change:

I1349T

Links:

dbSNP: rs80358654

NCBI 1000 Genomes Browser:

rs80358654

Molecular consequence:

NM_000059.4:c.4046T>C - 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
SCV000146363	Breast Cancer Information Core (BIC) (BRCA2)	no assertion criteria provided	Uncertain significance (May 29, 2002)	germline	clinical testing
SCV000244444	Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	reviewed by expert panel (ENIGMA BRCA1/2 Classification Criteria (2015))	Benign (Aug 10, 2015)	germline	curation	PubMed (1) [See all records that cite this PMID] ENIGMA BRCA1/2 Classification Criteria (2015), Citation Link,
SCV000488340	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Benign (Mar 3, 2016)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21990134, 17924331 Counsyl Autosomal Dominant Disease Classification criteria (2015) Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000146363

Breast Cancer Information Core (BIC) (BRCA2)

no assertion criteria provided

Uncertain significance
(May 29, 2002)

germline

clinical testing

SCV000244444

Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)

reviewed by expert panel

(ENIGMA BRCA1/2 Classification Criteria (2015))

Benign
(Aug 10, 2015)

germline

curation

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

ENIGMA BRCA1/2 Classification Criteria (2015),

Citation Link,

SCV000488340

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Dominant Disease Classification criteria (2015))

Benign
(Mar 3, 2016)

unknown

clinical testing

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

Counsyl Autosomal Dominant Disease Classification criteria (2015)

Citation Link

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	curation
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
Western European	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS).

Lindor NM, Guidugli L, Wang X, Vallée MP, Monteiro AN, Tavtigian S, Goldgar DE, Couch FJ.

Hum Mutat. 2012 Jan;33(1):8-21. doi: 10.1002/humu.21627. Epub 2011 Nov 3. Review.

PubMed [citation]

PMID:: 21990134
PMCID:: PMC3242438

A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes.

Easton DF, Deffenbaugh AM, Pruss D, Frye C, Wenstrup RJ, Allen-Brady K, Tavtigian SV, Monteiro AN, Iversen ES, Couch FJ, Goldgar DE.

Am J Hum Genet. 2007 Nov;81(5):873-83. Epub 2007 Sep 6.

PubMed [citation]

PMID:: 17924331
PMCID:: PMC2265654

Details of each submission

From Breast Cancer Information Core (BIC) (BRCA2), SCV000146363.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Western European	2	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	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

From Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), SCV000244444.1

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

Description

IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.0000088

#	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 Counsyl, SCV000488340.2

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

#	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

Last Updated: Jun 2, 2024

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