NM_000059.4(BRCA2):c.7820C>T (p.Thr2607Ile) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 11, 2022
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:: RCV000818024.6

Allele description [Variation Report for NM_000059.4(BRCA2):c.7820C>T (p.Thr2607Ile)]

NM_000059.4(BRCA2):c.7820C>T (p.Thr2607Ile)

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.7820C>T (p.Thr2607Ile)

HGVS:

NC_000013.11:g.32362537C>T
NG_012772.3:g.52058C>T
NM_000059.4:c.7820C>TMANE SELECT
NP_000050.2:p.Thr2607Ile
NP_000050.3:p.Thr2607Ile
LRG_293t1:c.7820C>T
LRG_293:g.52058C>T
LRG_293p1:p.Thr2607Ile
NC_000013.10:g.32936674C>T
NM_000059.3:c.7820C>T
p.Thr2607Ile

Protein change:

T2607I

Links:

dbSNP: rs1555286821

NCBI 1000 Genomes Browser:

rs1555286821

Molecular consequence:

NM_000059.4:c.7820C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary breast ovarian cancer syndrome
Synonyms:: Hereditary breast and ovarian cancer syndrome; Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000958616	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 11, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18060494, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000958616

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 11, 2022)

germline

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

Citations

PubMed

Twenty-three novel BRCA1 and BRCA2 sequence alterations in breast and/or ovarian cancer families of Eastern Spain.

Esteban Cardeñosa E, Bolufer Gilabert P, Palanca Suela S, Oltra Soler S, Barragán González E, Velasco Sampedro E, Chirivella González I, Segura Huerta A, Guillén Ponce C, Martínez de Dueñas E; Group for Assessment of Hereditary Cancer of Valencia Community..

Breast Cancer Res Treat. 2008 Nov;112(1):69-73. Epub 2007 Dec 1.

PubMed [citation]

PMID:: 18060494

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000958616.4

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

Description

This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 2607 of the BRCA2 protein (p.Thr2607Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 18060494). This variant is also known as 8048C>T. ClinVar contains an entry for this variant (Variation ID: 482993). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: May 7, 2024

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