NM_004333.6(BRAF):c.736G>C (p.Ala246Pro) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 2, 2013
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:: RCV000033285.6

Allele description

NM_004333.6(BRAF):c.736G>C (p.Ala246Pro)

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.736G>C (p.Ala246Pro)

Other names:

p.A246P:GCA>CCA; NM_004333.4(BRAF):c.736G>C

HGVS:

NC_000007.14:g.140801536C>G
NG_007873.3:g.128229G>C
NM_001354609.2:c.736G>C
NM_001374244.1:c.736G>C
NM_001374258.1:c.736G>C
NM_001378467.1:c.745G>C
NM_001378468.1:c.736G>C
NM_001378469.1:c.736G>C
NM_001378470.1:c.634G>C
NM_001378471.1:c.736G>C
NM_001378472.1:c.580G>C
NM_001378473.1:c.580G>C
NM_001378474.1:c.736G>C
NM_001378475.1:c.472G>C
NM_004333.6:c.736G>CMANE SELECT
NP_001341538.1:p.Ala246Pro
NP_001361173.1:p.Ala246Pro
NP_001361187.1:p.Ala246Pro
NP_001365396.1:p.Ala249Pro
NP_001365397.1:p.Ala246Pro
NP_001365398.1:p.Ala246Pro
NP_001365399.1:p.Ala212Pro
NP_001365400.1:p.Ala246Pro
NP_001365401.1:p.Ala194Pro
NP_001365402.1:p.Ala194Pro
NP_001365403.1:p.Ala246Pro
NP_001365404.1:p.Ala158Pro
NP_004324.2:p.Ala246Pro
LRG_299t1:c.736G>C
LRG_299:g.128229G>C
NC_000007.13:g.140501336C>G
NM_004333.4:c.736G>C
P15056:p.Ala246Pro

Protein change:

A158P; ALA246PRO

Links:

UniProtKB: P15056#VAR_026113; OMIM: 164757.0012; dbSNP: rs180177034

NCBI 1000 Genomes Browser:

rs180177034

Molecular consequence:

NM_001354609.2:c.736G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374244.1:c.736G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374258.1:c.736G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001378467.1:c.745G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001378468.1:c.736G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001378469.1:c.736G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001378470.1:c.634G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001378471.1:c.736G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001378472.1:c.580G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001378473.1:c.580G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001378474.1:c.736G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001378475.1:c.472G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004333.6:c.736G>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Noonan syndrome (NS)
Synonyms:: Noonan's syndrome; Pseudo-Turner syndrome
Identifiers:: MONDO: MONDO:0018997; MeSH: D009634; MedGen: C0028326; OMIM: PS163950

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000203919	Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Aug 2, 2013)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16474404, 17704260, 18456719, 18042262, 20523244, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000203919

Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Aug 2, 2013)

germline

clinical testing

PubMed (6)
[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	5	5	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

Cardio-facio-cutaneous and Noonan syndromes due to mutations in the RAS/MAPK signalling pathway: genotype-phenotype relationships and overlap with Costello syndrome.

Nava C, Hanna N, Michot C, Pereira S, Pouvreau N, Niihori T, Aoki Y, Matsubara Y, Arveiler B, Lacombe D, Pasmant E, Parfait B, Baumann C, Héron D, Sigaudy S, Toutain A, Rio M, Goldenberg A, Leheup B, Verloes A, Cavé H.

J Med Genet. 2007 Dec;44(12):763-71. Epub 2007 Aug 17.

PubMed [citation]

PMID:: 17704260
PMCID:: PMC2652823

See all PubMed Citations (6)

Details of each submission

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000203919.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	5	not provided	not provided	clinical testing	PubMed (6)

Description

The p.Ala246Pro variant in BRAF has been reported in 6 individuals with clinical features of Cardio-facio-cutaneous syndrome (CFC) (Niihori 2006, Nava 2007, Nys trom 2008, Schulz 2008, Ohtake 2011). This variant occurred de novo in 2 of thes e individuals (Niihori 2006, Schulz 2008), and one of these individuals also had Non-Hodgkin Lymphoma (Ohtake 2011). Furthermore, this variant has now been iden tified by our laboratory in 5 individuals with clinical features of Noonan syndr ome and/or CFC syndrome. It was also absent from large population studies. There fore, this variant meets our criteria to be classified as pathogenic (http://www .partners.org/personalizedmedicine/LMM).

#	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		5	not provided	5	not provided

Last Updated: Feb 20, 2022

ClinVar

Relating variation to medicine