NM_004333.6(BRAF):c.1379G>A (p.Gly460Glu) AND RASopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 21, 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:: RCV003655353.2

Allele description [Variation Report for NM_004333.6(BRAF):c.1379G>A (p.Gly460Glu)]

NM_004333.6(BRAF):c.1379G>A (p.Gly460Glu)

Gene:

BRAF:B-Raf proto-oncogene, serine/threonine kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q34

Genomic location:

Preferred name:

NM_004333.6(BRAF):c.1379G>A (p.Gly460Glu)

HGVS:

NC_000007.14:g.140781629C>T
NG_007873.3:g.148136G>A
NM_001354609.2:c.1379G>A
NM_001374244.1:c.1499G>A
NM_001374258.1:c.1499G>A
NM_001378467.1:c.1388G>A
NM_001378468.1:c.1379G>A
NM_001378469.1:c.1313G>A
NM_001378470.1:c.1277G>A
NM_001378471.1:c.1268G>A
NM_001378472.1:c.1223G>A
NM_001378473.1:c.1223G>A
NM_001378474.1:c.1379G>A
NM_001378475.1:c.1115G>A
NM_004333.6:c.1379G>AMANE SELECT
NP_001341538.1:p.Gly460Glu
NP_001361173.1:p.Gly500Glu
NP_001361187.1:p.Gly500Glu
NP_001365396.1:p.Gly463Glu
NP_001365397.1:p.Gly460Glu
NP_001365398.1:p.Gly438Glu
NP_001365399.1:p.Gly426Glu
NP_001365400.1:p.Gly423Glu
NP_001365401.1:p.Gly408Glu
NP_001365402.1:p.Gly408Glu
NP_001365403.1:p.Gly460Glu
NP_001365404.1:p.Gly372Glu
NP_004324.2:p.Gly460Glu
NP_004324.2:p.Gly460Glu
LRG_299t1:c.1379G>A
LRG_299:g.148136G>A
LRG_299p1:p.Gly460Glu
NC_000007.13:g.140481429C>T
NM_004333.4:c.1379G>A

Protein change:

G372E

Molecular consequence:

NM_001354609.2:c.1379G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374244.1:c.1499G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374258.1:c.1499G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378467.1:c.1388G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378468.1:c.1379G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378469.1:c.1313G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378470.1:c.1277G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378471.1:c.1268G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378472.1:c.1223G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378473.1:c.1223G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378474.1:c.1379G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378475.1:c.1115G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004333.6:c.1379G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: RASopathy
Synonyms:: rasopathies; Noonan spectrum disorder
Identifiers:: MONDO: MONDO:0021060; MedGen: C5555857

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004502638	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 21, 2023)	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

SCV004502638

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 21, 2023)

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, SCV004502638.1

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

Description

This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 460 of the BRAF protein (p.Gly460Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRAF-related conditions. ClinVar contains an entry for this variant (Variation ID: 1711752). 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 BRAF protein function with a negative predictive value of 80%. 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: Sep 29, 2024

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