NM_000059.4(BRCA2):c.9828A>T (p.Arg3276Ser) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 10, 2019
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000564446.6

Allele description [Variation Report for NM_000059.4(BRCA2):c.9828A>T (p.Arg3276Ser)]

NM_000059.4(BRCA2):c.9828A>T (p.Arg3276Ser)

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.9828A>T (p.Arg3276Ser)

HGVS:

NC_000013.11:g.32398341A>T
NG_012772.3:g.87862A>T
NM_000059.4:c.9828A>TMANE SELECT
NP_000050.2:p.Arg3276Ser
NP_000050.3:p.Arg3276Ser
LRG_293t1:c.9828A>T
LRG_293:g.87862A>T
LRG_293p1:p.Arg3276Ser
NC_000013.10:g.32972478A>T
NM_000059.3:c.9828A>T
U43746.1:n.10056A>T

Protein change:

R3276S

Links:

dbSNP: rs80359245

NCBI 1000 Genomes Browser:

rs80359245

Molecular consequence:

NM_000059.4:c.9828A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000665358	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 10, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001350583	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 21, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000665358

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 10, 2019)

germline

clinical testing

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

Citation Link,

SCV001350583

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 21, 2019)

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

Citations

PubMed

Global sequence diversity of BRCA2: analysis of 71 breast cancer families and 95 control individuals of worldwide populations.

Wagner TM, Hirtenlehner K, Shen P, Moeslinger R, Muhr D, Fleischmann E, Concin H, Doeller W, Haid A, Lang AH, Mayer P, Petru E, Ropp E, Langbauer G, Kubista E, Scheiner O, Underhill P, Mountain J, Stierer M, Zielinski C, Oefner P.

Hum Mol Genet. 1999 Mar;8(3):413-23. Erratum in: Hum Mol Genet 1999 Apr;8(4):717-9.

PubMed [citation]

PMID:: 9971877

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Ambry Genetics, SCV000665358.5

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

Description

The p.R3276S variant (also known as c.9828A>T), located in coding exon 26 of the BRCA2 gene, results from an A to T substitution at nucleotide position 9828. The arginine at codon 3276 is replaced by serine, an amino acid with dissimilar properties. This alteration was identified in the control population of a study looking for BRCA2 variants in breast and breast/ovarian cancer families (Wagner TM et al. Hum. Mol. Genet. 1999 Mar;8:413-23). This amino acid position is highly conserved through mammals but not in all available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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 Color Diagnostics, LLC DBA Color Health, SCV001350583.1

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

Last Updated: Sep 29, 2024

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