NM_000059.4(BRCA2):c.4258G>T (p.Asp1420Tyr) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:: Benign (14 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:: RCV000083103.28

Allele description [Variation Report for NM_000059.4(BRCA2):c.4258G>T (p.Asp1420Tyr)]

NM_000059.4(BRCA2):c.4258G>T (p.Asp1420Tyr)

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.4258G>T (p.Asp1420Tyr)

Other names:

p.D1420Y:GAT>TAT; NP_000050.3:p.Asp1420Tyr

HGVS:

NC_000013.11:g.32338613G>T
NG_012772.3:g.28134G>T
NM_000059.4:c.4258G>TMANE SELECT
NP_000050.2:p.Asp1420Tyr
NP_000050.3:p.Asp1420Tyr
LRG_293t1:c.4258G>T
LRG_293:g.28134G>T
LRG_293p1:p.Asp1420Tyr
NC_000013.10:g.32912750G>T
NM_000059.3:c.4258G>T
NM_000059.4:c.4258G>T
U43746.1:n.4486G>T
p.D1420Y

Nucleotide change:

4486G>T

Protein change:

D1420Y

Links:

dbSNP: rs28897727

NCBI 1000 Genomes Browser:

rs28897727

Molecular consequence:

NM_000059.4:c.4258G>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

205

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
SCV000115177	Sharing Clinical Reports Project (SCRP)	no assertion criteria provided	Benign (May 1, 2012)	germline	clinical testing
SCV000146395	Breast Cancer Information Core (BIC) (BRCA2)	no classification provided	not provided	germline	clinical testing
SCV000154044	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Likely benign (Jan 2, 2014)	unknown	literature only	PubMed (5) [See all records that cite these PMIDs] 21702907, 21952622, 22703879, 9971877, 21520273 Counsyl Autosomal Dominant Disease Classification criteria (2015), Citation Link,
SCV000187734	Pathway Genomics	no assertion criteria provided	Likely benign (Jul 24, 2014)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 22703879, 24728327, 12215251
SCV000195982	Michigan Medical Genetics Laboratories, University of Michigan	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Nov 3, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000244448	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,
SCV000383697	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Likely benign (Feb 12, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 9971877, 18607349 Citation Link,
SCV000575731	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Aug 26, 2015)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000733255	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Benign	germline	clinical testing
SCV000743297	Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus	criteria provided, single submitter (ACGS Guidelines, 2013)	Benign (Oct 9, 2014)	germline	clinical testing	Citation Link,
SCV000744454	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus	criteria provided, single submitter (ACGS Guidelines, 2013)	Benign (Sep 21, 2015)	germline	clinical testing	Citation Link,
SCV000863687	Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research - The Canadian Open Genetics Repository (COGR)	no assertion criteria provided	Likely benign	unknown	clinical testing
SCV001139086	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Likely benign (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV004016851	KCCC/NGS Laboratory, Kuwait Cancer Control Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Jul 7, 2023)	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	not provided	4	not provided	not provided	4	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, literature only, curation
not provided	germline	yes	129	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, literature only
Arab	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Ashkenazi	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing
Ashkenazi, Western European	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Austrian	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Caucasian	germline	yes	5	not provided	not provided	not provided	not provided	clinical testing
Central/Eastern European	germline	yes	4	not provided	not provided	not provided	not provided	clinical testing
German	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Irish German Dutch	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Latin American, Caribbean	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Native American	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing
Native American, Western European	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Western European	germline	yes	51	not provided	not provided	not provided	not provided	clinical testing
Western, Central/Eastern European	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A high-throughput protocol for mutation scanning of the BRCA1 and BRCA2 genes.

Hondow HL, Fox SB, Mitchell G, Scott RJ, Beshay V, Wong SQ; kConFab Investigators., Dobrovic A.

BMC Cancer. 2011 Jun 24;11:265. doi: 10.1186/1471-2407-11-265.

PubMed [citation]

PMID:: 21702907
PMCID:: PMC3146935

BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients.

Kote-Jarai Z, Leongamornlert D, Saunders E, Tymrakiewicz M, Castro E, Mahmud N, Guy M, Edwards S, O'Brien L, Sawyer E, Hall A, Wilkinson R, Dadaev T, Goh C, Easton D; UKGPCS Collaborators., Goldgar D, Eeles R.

Br J Cancer. 2011 Oct 11;105(8):1230-4. doi: 10.1038/bjc.2011.383. Epub 2011 Sep 27.

PubMed [citation]

PMID:: 21952622
PMCID:: PMC3208504

See all PubMed Citations (10)

Details of each submission

From Sharing Clinical Reports Project (SCRP), SCV000115177.3

#	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	4	not provided	not provided		not provided	not provided	not provided	not provided

From Breast Cancer Information Core (BIC) (BRCA2), SCV000146395.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	92	not provided	not provided	clinical testing	not provided
2	not provided	1	not provided	not provided	clinical testing	not provided
3	not provided	8	not provided	not provided	clinical testing	not provided
4	not provided	1	not provided	not provided	clinical testing	not provided
5	not provided	1	not provided	not provided	clinical testing	not provided
6	not provided	2	not provided	not provided	clinical testing	not provided
7	not provided	1	not provided	not provided	clinical testing	not provided
8	not provided	1	not provided	not provided	clinical testing	not provided
9	not provided	20	not provided	not provided	clinical testing	not provided
10	not provided	1	not provided	not provided	clinical testing	not provided
11	not provided	1	not provided	not provided	clinical testing	not provided
12	Arab	1	not provided	not provided	clinical testing	not provided
13	Ashkenazi	2	not provided	not provided	clinical testing	not provided
14	Ashkenazi, Western European	1	not provided	not provided	clinical testing	not provided
15	Austrian	1	not provided	not provided	clinical testing	not provided
16	Caucasian	2	not provided	not provided	clinical testing	not provided
17	Caucasian	2	not provided	not provided	clinical testing	not provided
18	Caucasian	1	not provided	not provided	clinical testing	not provided
19	Central/Eastern European	4	not provided	not provided	clinical testing	not provided
20	German	1	not provided	not provided	clinical testing	not provided
21	Irish German Dutch	1	not provided	not provided	clinical testing	not provided
22	Latin American, Caribbean	1	not provided	not provided	clinical testing	not provided
23	Native American	2	not provided	not provided	clinical testing	not provided
24	Native American, Western European	1	not provided	not provided	clinical testing	not provided
25	Western European	51	not provided	not provided	clinical testing	not provided
26	Western, Central/Eastern European	1	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		92	not provided	not provided	not provided
2	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
3	germline	yes	not provided	not provided	not provided		8	not provided	not provided	not provided
4	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
5	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
6	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided
7	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
8	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
9	germline	yes	not provided	not provided	not provided		20	not provided	not provided	not provided
10	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
11	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
12	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
13	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided
14	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
15	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
16	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided
17	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided
18	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
19	germline	yes	not provided	not provided	not provided		4	not provided	not provided	not provided
20	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
21	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
22	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
23	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided
24	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
25	germline	yes	not provided	not provided	not provided		51	not provided	not provided	not provided
26	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Counsyl, SCV000154044.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		not provided	not provided	not provided	literature only	PubMed (5)

#	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 Pathway Genomics, SCV000187734.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (3)

#	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 Michigan Medical Genetics Laboratories, University of Michigan, SCV000195982.1

#	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	yes	not provided	Blood	not provided		not provided	not provided	not provided	not provided

From Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), SCV000244448.1

#	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 = 0.000102

#	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 Illumina Laboratory Services, Illumina, SCV000383697.3

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

#	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 Fulgent Genetics, Fulgent Genetics, SCV000575731.1

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

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV000733255.1

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV000743297.1

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV000744454.1

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research - The Canadian Open Genetics Repository (COGR), SCV000863687.2

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Mendelics, SCV001139086.1

#	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 KCCC/NGS Laboratory, Kuwait Cancer Control Center, SCV004016851.1

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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