NM_004333.6(BRAF):c.1502A>G (p.Glu501Gly) AND Cardio-facio-cutaneous syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 21, 2011
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:: RCV000211750.4

Allele description [Variation Report for NM_004333.6(BRAF):c.1502A>G (p.Glu501Gly)]

NM_004333.6(BRAF):c.1502A>G (p.Glu501Gly)

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.1502A>G (p.Glu501Gly)

Other names:

p.E501G:GAA>GGA

HGVS:

NC_000007.14:g.140778006T>C
NG_007873.3:g.151759A>G
NM_001354609.2:c.1502A>G
NM_001374244.1:c.1622A>G
NM_001374258.1:c.1622A>G
NM_001378467.1:c.1511A>G
NM_001378468.1:c.1502A>G
NM_001378469.1:c.1436A>G
NM_001378470.1:c.1400A>G
NM_001378471.1:c.1391A>G
NM_001378472.1:c.1346A>G
NM_001378473.1:c.1346A>G
NM_001378474.1:c.1502A>G
NM_001378475.1:c.1238A>G
NM_004333.6:c.1502A>GMANE SELECT
NP_001341538.1:p.Glu501Gly
NP_001361173.1:p.Glu541Gly
NP_001361187.1:p.Glu541Gly
NP_001365396.1:p.Glu504Gly
NP_001365397.1:p.Glu501Gly
NP_001365398.1:p.Glu479Gly
NP_001365399.1:p.Glu467Gly
NP_001365400.1:p.Glu464Gly
NP_001365401.1:p.Glu449Gly
NP_001365402.1:p.Glu449Gly
NP_001365403.1:p.Glu501Gly
NP_001365404.1:p.Glu413Gly
NP_004324.2:p.Glu501Gly
LRG_299t1:c.1502A>G
LRG_299:g.151759A>G
NC_000007.13:g.140477806T>C
NM_004333.4:c.1502A>G
P15056:p.Glu501Gly
c.1502A>G

Protein change:

E413G; GLU501GLY

Links:

UniProtKB: P15056#VAR_026117; OMIM: 164757.0018; dbSNP: rs180177039

NCBI 1000 Genomes Browser:

rs180177039

Molecular consequence:

NM_001354609.2:c.1502A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374244.1:c.1622A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374258.1:c.1622A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378467.1:c.1511A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378468.1:c.1502A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378469.1:c.1436A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378470.1:c.1400A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378471.1:c.1391A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378472.1:c.1346A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378473.1:c.1346A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378474.1:c.1502A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001378475.1:c.1238A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_004333.6:c.1502A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Cardio-facio-cutaneous syndrome
Synonyms:: Cardiofaciocutaneous syndrome; CFC syndrome
Identifiers:: MONDO: MONDO:0015280; MedGen: C1275081; Orphanet: 1340; OMIM: PS115150

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LOC130003116 [Homo sapiens]
LOC130003116 [Homo sapiens]
Gene ID:130003116

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000061587	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Nov 21, 2011)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16474404, 16439621, 17366577, 18413255, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000061587

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Nov 21, 2011)

germline

clinical testing

PubMed (5)
[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	not provided	1	1	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

Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome.

Rodriguez-Viciana P, Tetsu O, Tidyman WE, Estep AL, Conger BA, Cruz MS, McCormick F, Rauen KA.

Science. 2006 Mar 3;311(5765):1287-90. Epub 2006 Jan 26.

PubMed [citation]

PMID:: 16439621

See all PubMed Citations (5)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000061587.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (5)

Description

The Glu501Gly variant has been reported in at least 7 individuals with clinical features of Cardio-facio-cutaneous syndrome and was absent from 280 control chro mosomes (Niihori 2006, Rodriguez-Viciana 2006, Narumi 2007, Rodriguez-Viciana 20 08). In addition, this variant was reported to have occurred de novo in two indi viduals, supporting a pathogenic role. Furthermore, glutamic acid (Glu) at posi tion 501 is highly conserved across evolutionarily distant species into C. elega ns and computational analyses (AlignGVGD, PolyPhen2, SIFT) predict that a change to a glycine (Gly) at this position may impact the protein. Based on this info rmation, this variant is highly likely to be pathogenic. The presence of a heter ozygous pathogenic variant in BRAF is consistent with a diagnosis of Cardio-faci o-cutaneous syndrome but this information should be reconciled with the complete clinical history of this individual.

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

Last Updated: Sep 29, 2024

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