NM_000059.4(BRCA2):c.4289C>T (p.Thr1430Ile) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 8, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003477733.1

Allele description [Variation Report for NM_000059.4(BRCA2):c.4289C>T (p.Thr1430Ile)]

NM_000059.4(BRCA2):c.4289C>T (p.Thr1430Ile)

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.4289C>T (p.Thr1430Ile)

HGVS:

NC_000013.11:g.32338644C>T
NG_012772.3:g.28165C>T
NM_000059.4:c.4289C>TMANE SELECT
NP_000050.2:p.Thr1430Ile
NP_000050.3:p.Thr1430Ile
LRG_293t1:c.4289C>T
LRG_293:g.28165C>T
LRG_293p1:p.Thr1430Ile
NC_000013.10:g.32912781C>T
NM_000059.3:c.4289C>T

Protein change:

T1430I

Links:

dbSNP: rs876659247

NCBI 1000 Genomes Browser:

rs876659247

Molecular consequence:

NM_000059.4:c.4289C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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SPFH domain-containing protein [Streptococcus pneumoniae]
SPFH domain-containing protein [Streptococcus pneumoniae]
gi|2720098295|gnl|PRJNA1000275|Q762 00|gb|WZQ52248.1|

Protein
Homo sapiens genomic DNA; cDNA DKFZp761E2423 (from clone DKFZp761E2423)
Homo sapiens genomic DNA; cDNA DKFZp761E2423 (from clone DKFZp761E2423)
gi|7018482|emb|AL157466.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004219626	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Jun 8, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31911673, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004219626

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Jun 8, 2023)

unknown

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Systematic misclassification of missense variants in BRCA1 and BRCA2 "coldspots".

Dines JN, Shirts BH, Slavin TP, Walsh T, King MC, Fowler DM, Pritchard CC.

Genet Med. 2020 May;22(5):825-830. doi: 10.1038/s41436-019-0740-6. Epub 2020 Jan 8.

PubMed [citation]

PMID:: 31911673
PMCID:: PMC7200594

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, SCV004219626.1

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

Description

In the published literature, this variant has been identified in a study of BRCA1 and BRCA2 regions without essential functions that tolerate variation (PMID: 31911673 (2020)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

#	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

Last Updated: Sep 1, 2024

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