NM_000059.4(BRCA2):c.2471T>G (p.Leu824Ter) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Feb 6, 2024
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:: RCV000506370.12

Allele description [Variation Report for NM_000059.4(BRCA2):c.2471T>G (p.Leu824Ter)]

NM_000059.4(BRCA2):c.2471T>G (p.Leu824Ter)

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.2471T>G (p.Leu824Ter)

Other names:

2699T>G

HGVS:

NC_000013.11:g.32336826T>G
NG_012772.3:g.26347T>G
NM_000059.4:c.2471T>GMANE SELECT
NP_000050.2:p.Leu824Ter
NP_000050.3:p.Leu824Ter
LRG_293t1:c.2471T>G
LRG_293:g.26347T>G
LRG_293p1:p.Leu824Ter
NC_000013.10:g.32910963T>G
NM_000059.3:c.2471T>G
p.Leu824*
p.Leu824X

Protein change:

L824*

Links:

dbSNP: rs397507631

NCBI 1000 Genomes Browser:

rs397507631

Molecular consequence:

NM_000059.4:c.2471T>G - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000600513	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (May 4, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22762150, 26467025
SCV000617464	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Oct 6, 2017)	germline	clinical testing	Citation Link,
SCV004242882	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 6, 2024)	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

SCV000600513

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(May 4, 2017)

germline

clinical testing

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

SCV000617464

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Oct 6, 2017)

germline

clinical testing

Citation Link,

SCV004242882

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 6, 2024)

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	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

Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1 and BRCA2 mutations carrier cohort (GENEPSO).

Lecarpentier J, Noguès C, Mouret-Fourme E, Gauthier-Villars M, Lasset C, Fricker JP, Caron O, Stoppa-Lyonnet D, Berthet P, Faivre L, Bonadona V, Buecher B, Coupier I, Gladieff L, Gesta P, Eisinger F, Frénay M, Luporsi E, Lortholary A, Colas C, Dugast C, Longy M, et al.

Breast Cancer Res. 2012 Jul 3;14(4):R99. doi: 10.1186/bcr3218.

PubMed [citation]

PMID:: 22762150
PMCID:: PMC3680948

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

See all PubMed Citations (3)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000600513.2

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

From GeneDx, SCV000617464.2

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

Description

This variant is denoted BRCA2 c.2471T>G at the cDNA level and p.Leu824Ter (L824X) at the proteinlevel. Using alternate nomenclature, this variant would be defined as BRCA2 2699T>G. The substitution creates anonsense variant, which changes a Leucine to a premature stop codon (TTA>TGA), and is predicted to cause loss ofnormal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has beenreported as a pathogenic variant in one French family, however, no clinical information was provided (Lecarpentier2012). Based on currently available information, we consider this variant to be pathogenic

#	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 Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, SCV004242882.1

#	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: Nov 10, 2024

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