NM_000059.4(BRCA2):c.3824T>C (p.Ile1275Thr) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 20, 2022
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:: RCV000985512.5

Allele description [Variation Report for NM_000059.4(BRCA2):c.3824T>C (p.Ile1275Thr)]

NM_000059.4(BRCA2):c.3824T>C (p.Ile1275Thr)

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.3824T>C (p.Ile1275Thr)

HGVS:

NC_000013.11:g.32338179T>C
NG_012772.3:g.27700T>C
NM_000059.4:c.3824T>CMANE SELECT
NP_000050.2:p.Ile1275Thr
NP_000050.3:p.Ile1275Thr
LRG_293t1:c.3824T>C
LRG_293:g.27700T>C
LRG_293p1:p.Ile1275Thr
NC_000013.10:g.32912316T>C
NM_000059.3:c.3824T>C
U43746.1:n.4052T>C
p.I1275T

Nucleotide change:

4052T>C

Protein change:

I1275T

Links:

dbSNP: rs80358625

NCBI 1000 Genomes Browser:

rs80358625

Molecular consequence:

NM_000059.4:c.3824T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001133772	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Oct 1, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25896959, 26467025
SCV002008973	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Oct 20, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001133772

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Oct 1, 2018)

germline

clinical testing

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

SCV002008973

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Oct 20, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	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

The molecular analysis of BRCA1 and BRCA2: Next-generation sequencing supersedes conventional approaches.

D'Argenio V, Esposito MV, Telese A, Precone V, Starnone F, Nunziato M, Cantiello P, Iorio M, Evangelista E, D'Aiuto M, Calabrese A, Frisso G, D'Aiuto G, Salvatore F.

Clin Chim Acta. 2015 Jun 15;446:221-5. doi: 10.1016/j.cca.2015.03.045. Epub 2015 Apr 17.

PubMed [citation]

PMID:: 25896959

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001133772.3

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

From GeneDx, SCV002008973.3

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

Description

Observed in individuals with a personal history of breast cancer (D'Argenio et al., 2015); In silico analysis supports that this missense variant does not alter protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 4052T>C; This variant is associated with the following publications: (PMID: 31131967, 28843361, 25896959)

#	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: Apr 20, 2024

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