NM_000059.4(BRCA2):c.4261T>C (p.Phe1421Leu) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 1, 2016
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:: RCV000231637.7

Allele description [Variation Report for NM_000059.4(BRCA2):c.4261T>C (p.Phe1421Leu)]

NM_000059.4(BRCA2):c.4261T>C (p.Phe1421Leu)

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.4261T>C (p.Phe1421Leu)

HGVS:

NC_000013.11:g.32338616T>C
NG_012772.3:g.28137T>C
NM_000059.4:c.4261T>CMANE SELECT
NP_000050.2:p.Phe1421Leu
NP_000050.3:p.Phe1421Leu
LRG_293t1:c.4261T>C
LRG_293:g.28137T>C
LRG_293p1:p.Phe1421Leu
NC_000013.10:g.32912753T>C
NM_000059.3:c.4261T>C

Protein change:

F1421L

Links:

dbSNP: rs878853582

NCBI 1000 Genomes Browser:

rs878853582

Molecular consequence:

NM_000059.4:c.4261T>C - 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

Recent activity

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zinc finger SWIM domain-containing protein 7 [Mus musculus]
zinc finger SWIM domain-containing protein 7 [Mus musculus]
gi|254553350|ref|NP_081474.1|

Protein
Rattus norvegicus carbonyl reductase 1 (Cbr1), mRNA
Rattus norvegicus carbonyl reductase 1 (Cbr1), mRNA
gi|2443977978|ref|NM_019170.3|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000283235	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 1, 2016)	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

SCV000283235

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 1, 2016)

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

Citations

PubMed

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000283235.5

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

Description

The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. In addition, algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this is a novel missense change that is not predicted to affect protein function or cause disease. However the evidence is insufficient at this time to prove that conclusively. It has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA2-related disease. This sequence change replaces phenylalanine with leucine at codon 1421 of the BRCA2 protein (p.Phe1421Leu). The phenylalanine residue is weakly conserved and there is a small physicochemical difference between phenylalanine and leucine.

#	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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