NM_004333.6(BRAF):c.1495A>G (p.Lys499Glu) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Dec 2, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000207517.9

Allele description [Variation Report for NM_004333.6(BRAF):c.1495A>G (p.Lys499Glu)]

NM_004333.6(BRAF):c.1495A>G (p.Lys499Glu)

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.1495A>G (p.Lys499Glu)

Other names:

p.K499E:AAA>GAA

HGVS:

NC_000007.14:g.140778013T>C
NG_007873.3:g.151752A>G
NM_001354609.2:c.1495A>G
NM_001374244.1:c.1615A>G
NM_001374258.1:c.1615A>G
NM_001378467.1:c.1504A>G
NM_001378468.1:c.1495A>G
NM_001378469.1:c.1429A>G
NM_001378470.1:c.1393A>G
NM_001378471.1:c.1384A>G
NM_001378472.1:c.1339A>G
NM_001378473.1:c.1339A>G
NM_001378474.1:c.1495A>G
NM_001378475.1:c.1231A>G
NM_004333.6:c.1495A>GMANE SELECT
NP_001341538.1:p.Lys499Glu
NP_001361173.1:p.Lys539Glu
NP_001361187.1:p.Lys539Glu
NP_001365396.1:p.Lys502Glu
NP_001365397.1:p.Lys499Glu
NP_001365398.1:p.Lys477Glu
NP_001365399.1:p.Lys465Glu
NP_001365400.1:p.Lys462Glu
NP_001365401.1:p.Lys447Glu
NP_001365402.1:p.Lys447Glu
NP_001365403.1:p.Lys499Glu
NP_001365404.1:p.Lys411Glu
NP_004324.2:p.Lys499Glu
LRG_299t1:c.1495A>G
LRG_299:g.151752A>G
NC_000007.13:g.140477813T>C
NM_004333.4:c.1495A>G
NM_004333.6:c.1495A>G
P15056:p.Lys499Glu

Protein change:

K411E; LYS499GLU

Links:

UniProtKB: P15056#VAR_026116; OMIM: 164757.0016; dbSNP: rs180177037

NCBI 1000 Genomes Browser:

rs180177037

Molecular consequence:

NM_001354609.2:c.1495A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374244.1:c.1615A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374258.1:c.1615A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378467.1:c.1504A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378468.1:c.1495A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378469.1:c.1429A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378470.1:c.1393A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378471.1:c.1384A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378472.1:c.1339A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378473.1:c.1339A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378474.1:c.1495A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378475.1:c.1231A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_004333.6:c.1495A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000057217	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Dec 2, 2023)	germline	clinical testing	Citation Link,
SCV000263063	Molecular Diagnostics Lab, Nemours Children's Health, Delaware	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jul 23, 2015)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16474404, 18042262, 16439621, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000057217

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Dec 2, 2023)

germline

clinical testing

Citation Link,

SCV000263063

Molecular Diagnostics Lab, Nemours Children's Health, Delaware

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jul 23, 2015)

unknown

clinical testing

PubMed (4)
[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	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome.

Niihori T, Aoki Y, Narumi Y, Neri G, Cavé H, Verloes A, Okamoto N, Hennekam RC, Gillessen-Kaesbach G, Wieczorek D, Kavamura MI, Kurosawa K, Ohashi H, Wilson L, Heron D, Bonneau D, Corona G, Kaname T, Naritomi K, Baumann C, Matsumoto N, Kato K, et al.

Nat Genet. 2006 Mar;38(3):294-6. Epub 2006 Feb 12.

PubMed [citation]

PMID:: 16474404

Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome.

Schulz AL, Albrecht B, Arici C, van der Burgt I, Buske A, Gillessen-Kaesbach G, Heller R, Horn D, Hübner CA, Korenke GC, König R, Kress W, Krüger G, Meinecke P, Mücke J, Plecko B, Rossier E, Schinzel A, Schulze A, Seemanova E, Seidel H, Spranger S, et al.

Clin Genet. 2008 Jan;73(1):62-70. Epub 2007 Nov 27.

PubMed [citation]

PMID:: 18042262

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000057217.15

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22824468, 23505473, 18456719, 34184824, 18413255, 23093928, 16474404, 18042262, 19376813, 24803665, 16439621, 30462361, 31560489, 32369273, 28404629)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Molecular Diagnostics Lab, Nemours Children's Health, Delaware, SCV000263063.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (4)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Jul 23, 2024

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