NM_004333.6(BRAF):c.1406G>A (p.Gly469Glu) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jun 13, 2022
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:: RCV000212152.13

Allele description [Variation Report for NM_004333.6(BRAF):c.1406G>A (p.Gly469Glu)]

NM_004333.6(BRAF):c.1406G>A (p.Gly469Glu)

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.1406G>A (p.Gly469Glu)

Other names:

p.G469E:GGA>GAA; NM_004333.5(BRAF):c.1406G>A; NM_004333.6(BRAF):c.1406G>A

HGVS:

NC_000007.14:g.140781602C>T
NG_007873.3:g.148163G>A
NM_001354609.2:c.1406G>A
NM_001374244.1:c.1526G>A
NM_001374258.1:c.1526G>A
NM_001378467.1:c.1415G>A
NM_001378468.1:c.1406G>A
NM_001378469.1:c.1340G>A
NM_001378470.1:c.1304G>A
NM_001378471.1:c.1295G>A
NM_001378472.1:c.1250G>A
NM_001378473.1:c.1250G>A
NM_001378474.1:c.1406G>A
NM_001378475.1:c.1142G>A
NM_004333.6:c.1406G>AMANE SELECT
NP_001341538.1:p.Gly469Glu
NP_001361173.1:p.Gly509Glu
NP_001361187.1:p.Gly509Glu
NP_001365396.1:p.Gly472Glu
NP_001365397.1:p.Gly469Glu
NP_001365398.1:p.Gly447Glu
NP_001365399.1:p.Gly435Glu
NP_001365400.1:p.Gly432Glu
NP_001365401.1:p.Gly417Glu
NP_001365402.1:p.Gly417Glu
NP_001365403.1:p.Gly469Glu
NP_001365404.1:p.Gly381Glu
NP_004324.2:p.Gly469Glu
LRG_299t1:c.1406G>A
LRG_299:g.148163G>A
NC_000007.13:g.140481402C>T
NM_001374258.1:c.1526G>A
NM_004333.4:c.1406G>A
NM_004333.5:c.1406G>A
P15056:p.Gly469Glu
c.1406G>A

Protein change:

G381E; GLY469GLU

Links:

UniProtKB: P15056#VAR_018621; OMIM: 164757.0014; dbSNP: rs121913355

NCBI 1000 Genomes Browser:

rs121913355

Molecular consequence:

NM_001354609.2:c.1406G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374244.1:c.1526G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374258.1:c.1526G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378467.1:c.1415G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378468.1:c.1406G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378469.1:c.1340G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378470.1:c.1304G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378471.1:c.1295G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378472.1:c.1250G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378473.1:c.1250G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378474.1:c.1406G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378475.1:c.1142G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004333.6:c.1406G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Papio anubis tripartite motif-containing 5 alpha (TRIM5) mRNA, complete cds
Papio anubis tripartite motif-containing 5 alpha (TRIM5) mRNA, complete cds
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Nucleotide
Sapporo virus capsid protein mRNA, partial cds.
Sapporo virus capsid protein mRNA, partial cds.
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000057212	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 13, 2022)	germline	clinical testing	Citation Link,
SCV000225337	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Jul 27, 2014)	germline	clinical testing	Citation Link,
SCV001714860	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 23, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18042262, 16474404, 29907801, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000057212

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jun 13, 2022)

germline

clinical testing

Citation Link,

SCV000225337

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(Jul 27, 2014)

germline

clinical testing

Citation Link,

SCV001714860

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 23, 2020)

germline

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	germline	unknown	2	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

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

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

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000057212.16

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

Description

Published functional studies demonstrate a damaging effect on B-Raf activity and MEK and ERK phosphorylation (Rodriguez-Viciana et al., 2006); Missense variants in this gene are often considered pathogenic (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); 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: 23093928, 34573299, 30141192, 34184824, 29907801, 18042262, 16474404, 16439621, 19206169, 24803665, 33040082)

#	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 Eurofins Ntd Llc (ga), SCV000225337.5

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

#	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		1	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV001714860.1

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

Description

PP2, PP3, PM1, PM2, PS2_VeryStrong, PS3

#	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		1	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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