NM_004333.6(BRAF):c.1455G>C (p.Leu485Phe) AND Ataxia-telangiectasia syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 5, 2022
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:: RCV001849264.11

Allele description [Variation Report for NM_004333.6(BRAF):c.1455G>C (p.Leu485Phe)]

NM_004333.6(BRAF):c.1455G>C (p.Leu485Phe)

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.1455G>C (p.Leu485Phe)

HGVS:

NC_000007.14:g.140778053C>G
NG_007873.3:g.151712G>C
NM_001354609.2:c.1455G>C
NM_001374244.1:c.1575G>C
NM_001374258.1:c.1575G>C
NM_001378467.1:c.1464G>C
NM_001378468.1:c.1455G>C
NM_001378469.1:c.1389G>C
NM_001378470.1:c.1353G>C
NM_001378471.1:c.1344G>C
NM_001378472.1:c.1299G>C
NM_001378473.1:c.1299G>C
NM_001378474.1:c.1455G>C
NM_001378475.1:c.1191G>C
NM_004333.6:c.1455G>CMANE SELECT
NP_001341538.1:p.Leu485Phe
NP_001361173.1:p.Leu525Phe
NP_001361187.1:p.Leu525Phe
NP_001365396.1:p.Leu488Phe
NP_001365397.1:p.Leu485Phe
NP_001365398.1:p.Leu463Phe
NP_001365399.1:p.Leu451Phe
NP_001365400.1:p.Leu448Phe
NP_001365401.1:p.Leu433Phe
NP_001365402.1:p.Leu433Phe
NP_001365403.1:p.Leu485Phe
NP_001365404.1:p.Leu397Phe
NP_004324.2:p.Leu485Phe
NP_004324.2:p.Leu485Phe
LRG_299t1:c.1455G>C
LRG_299:g.151712G>C
NC_000007.13:g.140477853C>G
NM_004333.4:c.1455G>C
NM_004333.6(BRAF):c.1455G>CMANE SELECT
P15056:p.Leu485Phe

Protein change:

L397F; LEU485PHE

Links:

UniProtKB: P15056#VAR_026115; OMIM: 164757.0015; dbSNP: rs180177036

NCBI 1000 Genomes Browser:

rs180177036

Molecular consequence:

NM_001354609.2:c.1455G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374244.1:c.1575G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374258.1:c.1575G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001378467.1:c.1464G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001378468.1:c.1455G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001378469.1:c.1389G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001378470.1:c.1353G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001378471.1:c.1344G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001378472.1:c.1299G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001378473.1:c.1299G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001378474.1:c.1455G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001378475.1:c.1191G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004333.6:c.1455G>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Ataxia-telangiectasia syndrome (AT)
Synonyms:: Louis-Bar syndrome; Cerebello-oculocutaneous telangiectasia; Immunodeficiency with ataxia telangiectasia; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008840; MedGen: C0004135; Orphanet: 100; OMIM: 208900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002107090	DASA	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 5, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 18413255, 19206169, 18953432, 18039235, 16474404, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002107090

DASA

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 5, 2022)

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	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Biochemical characterization of novel germline BRAF and MEK mutations in cardio-facio-cutaneous syndrome.

Rodriguez-Viciana P, Rauen KA.

Methods Enzymol. 2008;438:277-89. doi: 10.1016/S0076-6879(07)38019-1.

PubMed [citation]

PMID:: 18413255

Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum.

Sarkozy A, Carta C, Moretti S, Zampino G, Digilio MC, Pantaleoni F, Scioletti AP, Esposito G, Cordeddu V, Lepri F, Petrangeli V, Dentici ML, Mancini GM, Selicorni A, Rossi C, Mazzanti L, Marino B, Ferrero GB, Silengo MC, Memo L, Stanzial F, Faravelli F, et al.

Hum Mutat. 2009 Apr;30(4):695-702. doi: 10.1002/humu.20955.

PubMed [citation]

PMID:: 19206169
PMCID:: PMC4028130

See all PubMed Citations (6)

Details of each submission

From DASA, SCV002107090.2

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

Description

Same amino acid change as a previously established pathogenic variant regardless of nucleotide change (ClinVar ID: 177844 - c.1575G>T;p.(Leu525Phe)) PS1.Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID: 18413255; 18953432) - PS3_moderate.The c.1455G>C;p.(Leu485Phe) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 13975; PMID: 19206169; PMID: 18953432; PMID: 18039235; PMID: 16474404) - PS4. The variant is located in a mutational hot spot and/or critical and well-established functional domain (Pkinase_Tyr) - PM1. This variant is not present in population databases (rs180177036- gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. Pathogenic missense variant in this residue have been reported (ClinVar ID: 40370) - PM5. The variant was assumed de novo, but without confirmation of paternity and maternity (PMID: 19206169) - PM6. Missense variant in BRAF that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease - PP2. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is pathogenic.

#	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		1	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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