NM_000059.4(BRCA2):c.2585A>G (p.Lys862Arg) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 31, 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:: RCV001315760.7

Allele description [Variation Report for NM_000059.4(BRCA2):c.2585A>G (p.Lys862Arg)]

NM_000059.4(BRCA2):c.2585A>G (p.Lys862Arg)

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.2585A>G (p.Lys862Arg)

HGVS:

NC_000013.11:g.32336940A>G
NG_012772.3:g.26461A>G
NM_000059.4:c.2585A>GMANE SELECT
NP_000050.2:p.Lys862Arg
NP_000050.3:p.Lys862Arg
LRG_293t1:c.2585A>G
LRG_293:g.26461A>G
LRG_293p1:p.Lys862Arg
NC_000013.10:g.32911077A>G
NM_000059.3:c.2585A>G

Protein change:

K862R

Links:

dbSNP: rs876659257

NCBI 1000 Genomes Browser:

rs876659257

Molecular consequence:

NM_000059.4:c.2585A>G - 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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Homo sapiens ankyrin repeat and sterile alpha motif domain containing 4B (ANKS4B...
Homo sapiens ankyrin repeat and sterile alpha motif domain containing 4B (ANKS4B), mRNA
gi|1519246130|ref|NM_145865.3|

Nucleotide
Borassodendron machadonis
Borassodendron machadonis
Borassodendron machadonis RefSeq Genome

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001506350	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 31, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 31907386, 33078592, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001506350

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 31, 2022)

germline

clinical testing

PubMed (3)
[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

Impact of proactive high-throughput functional assay data on BRCA1 variant interpretation in 3684 patients with breast or ovarian cancer.

Kim HK, Lee EJ, Lee YJ, Kim J, Kim Y, Kim K, Lee SW, Chang S, Lee YJ, Lee JW, Lee W, Chun S, Son BH, Jung KH, Kim YM, Min WK, Ahn SH.

J Hum Genet. 2020 Mar;65(3):209-220. doi: 10.1038/s10038-019-0713-2. Epub 2020 Jan 6.

PubMed [citation]

PMID:: 31907386

Reclassification of BRCA1 and BRCA2 variants found in ovarian epithelial, fallopian tube, and primary peritoneal cancers.

Ha HI, Ryu JS, Shim H, Kong SY, Lim MC.

J Gynecol Oncol. 2020 Nov;31(6):e83. doi: 10.3802/jgo.2020.31.e83.

PubMed [citation]

PMID:: 33078592
PMCID:: PMC7593220

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001506350.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

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. 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. ClinVar contains an entry for this variant (Variation ID: 231603). This missense change has been observed in individual(s) with BRCA2-related cancers (PMID: 31907386, 33078592). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 862 of the BRCA2 protein (p.Lys862Arg).

#	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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