NM_000059.4(BRCA2):c.2926_2927delinsAT (p.Ser976Ile) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: May 2, 2016
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:: RCV000586739.17

Allele description [Variation Report for NM_000059.4(BRCA2):c.2926_2927delinsAT (p.Ser976Ile)]

NM_000059.4(BRCA2):c.2926_2927delinsAT (p.Ser976Ile)

Gene:

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

Variant type:

Indel

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.2926_2927delinsAT (p.Ser976Ile)

Other names:

p.S976I:TCC>ATC

HGVS:

NC_000013.11:g.32337281_32337282delinsAT
NG_012772.3:g.26802_26803delinsAT
NM_000059.4:c.2926_2927delinsATMANE SELECT
NP_000050.3:p.Ser976Ile
LRG_293:g.26802_26803delinsAT
NC_000013.10:g.32911418_32911419delinsAT
NM_000059.3:c.2926_2927delTCinsAT
NM_000059.4:c.2926_2927delinsAT
U43746.1:n.3154_3155delTCinsAT
p.S976I

Protein change:

S976I

Links:

dbSNP: rs276174831

NCBI 1000 Genomes Browser:

rs276174831

Molecular consequence:

NM_000059.4:c.2926_2927delinsAT - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000225170	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (Sep 8, 2014)	germline	clinical testing	Citation Link,
SCV000694650	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (May 2, 2016)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16030099, 12491487, 18284688, 23929434, 24728327 LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000225170

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Uncertain significance
(Sep 8, 2014)

germline

clinical testing

Citation Link,

SCV000694650

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(May 2, 2016)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Prevalence of BRCA mutations and founder effect in high-risk Hispanic families.

Weitzel JN, Lagos V, Blazer KR, Nelson R, Ricker C, Herzog J, McGuire C, Neuhausen S.

Cancer Epidemiol Biomarkers Prev. 2005 Jul;14(7):1666-71.

PubMed [citation]

PMID:: 16030099

Breast cancer genetics in African Americans.

Olopade OI, Fackenthal JD, Dunston G, Tainsky MA, Collins F, Whitfield-Broome C.

Cancer. 2003 Jan 1;97(1 Suppl):236-45. Review.

PubMed [citation]

PMID:: 12491487

See all PubMed Citations (5)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000225170.5

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000694650.1

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

Description

Variant summary: The c.2926_2927delinsAT variant involves the alteration of two nucleotides resulting in an amino acid change from Ser to Ile. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.073%, predominantly observed in the African subpopulation at a frequency of 0.85%. This frequency exceeds the maximal expected allele frequency for a pathogenic variant in BRCA2 (0.075%) by 11-fold, suggesting this is a benign polymorphism found primarily in population(s) of African origin. The variant has been reported in patients and controls in the literature and has been classified by multiple reputable clinical labs as "benign". Additionally, the variant was found to co-occur with pathogenic variants from several databases: BRCA1 c.3817C>T, p.Gln1273X (UMD); BRCA2 c.9026_9030delATCAT, p.Tyr3009_His3010?fs (BIC); BRCA1 c.815_824dupAGCCATGTGG, p.Thr276Alafs (BIC). Taken together, this variant has been classified as a 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

Last Updated: Nov 10, 2024

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