NM_001374258.1(BRAF):c.83GCGCCG[1] (p.28GA[1]) AND Rasopathy

Clinical significance:Uncertain significance (Last evaluated: Jul 21, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000033270.5

Allele description [Variation Report for NM_001374258.1(BRAF):c.83GCGCCG[1] (p.28GA[1])]

NM_001374258.1(BRAF):c.83GCGCCG[1] (p.28GA[1])

Gene:
BRAF:B-Raf proto-oncogene, serine/threonine kinase [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
7q34
Genomic location:
Preferred name:
NM_001374258.1(BRAF):c.83GCGCCG[1] (p.28GA[1])
HGVS:
  • NC_000007.14:g.140924608GCCGGC[1]
  • NG_007873.3:g.5144GCGCCG[1]
  • NM_001354609.2:c.83GCGCCG[1]
  • NM_001374244.1:c.83GCGCCG[1]
  • NM_001374258.1:c.83GCGCCG[1]MANE SELECT
  • NM_001378467.1:c.83GCGCCG[1]
  • NM_001378468.1:c.83GCGCCG[1]
  • NM_001378469.1:c.83GCGCCG[1]
  • NM_001378470.1:c.83GCGCCG[1]
  • NM_001378471.1:c.83GCGCCG[1]
  • NM_001378474.1:c.83GCGCCG[1]
  • NM_001378475.1:c.83GCGCCG[1]
  • NM_004333.6:c.83GCGCCG[1]
  • NP_001341538.1:p.28GA[1]
  • NP_001361173.1:p.28GA[1]
  • NP_001361187.1:p.28GA[1]
  • NP_001365396.1:p.28GA[1]
  • NP_001365397.1:p.28GA[1]
  • NP_001365398.1:p.28GA[1]
  • NP_001365399.1:p.28GA[1]
  • NP_001365400.1:p.28GA[1]
  • NP_001365403.1:p.28GA[1]
  • NP_001365404.1:p.28GA[1]
  • NP_004324.2:p.28GA[1]
  • NP_004324.2:p.Gly30_Ala33del
  • NP_004324.2:p.Gly30_Ala33del
  • LRG_299t1:c.89_100del
  • LRG_299:g.5144GCGCCG[1]
  • LRG_299p1:p.Gly30_Ala33del
  • NC_000007.13:g.140624404_140624415del
  • NC_000007.13:g.140624408GCCGGC[1]
  • NM_004333.4:c.89_100delGCGCCGGCGCCG
  • NM_004333.6:c.89_100delGCGCCGGCGCCG
  • p.G30_A33delGAGA
Links:
dbSNP: rs397507458
NCBI 1000 Genomes Browser:
rs397507458
Molecular consequence:
  • NM_001354609.2:c.83GCGCCG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001374244.1:c.83GCGCCG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001374258.1:c.83GCGCCG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001378467.1:c.83GCGCCG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001378468.1:c.83GCGCCG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001378469.1:c.83GCGCCG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001378470.1:c.83GCGCCG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001378471.1:c.83GCGCCG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001378474.1:c.83GCGCCG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001378475.1:c.83GCGCCG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_004333.6:c.83GCGCCG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:
Rasopathy
Synonyms:
rasopathies; Noonan spectrum disorder
Identifiers:
MONDO: MONDO:0021060; MedGen: CN166718

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000057175GeneDxcriteria provided, single submitter
Uncertain significance
(Jan 29, 2014)
germlineclinical testing

Citation Link,

SCV001489359Invitaecriteria provided, single submitter
Uncertain significance
(Jul 21, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From GeneDx, SCV000057175.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

c.89_100del12: p.Gly30_Ala33delGlyAlaGlyAla (G30_A33delGAGA) in exon 1 of the BRAF gene (NM_004333.4)The c.89_100del12 in-frame deletion in the BRAF gene has not been reported as a disease-causing mutation, nor is it known to be a benign polymorphism to our knowledge. This deletion occurs in a region of the protein that is not highly conserved in mammals and no disease-causing mutation has been reported before codon Threonine 241. Most disease-causing mutations result in a gain-of-function. It is uncertain if this deletion would result in a gain-of-function, loss-of-function, or have no impact on protein function at all. Therefore, this variant cannot be interpreted for diagnosis or used for genetic counseling without further studies. The variant is found in NOONAN panel(s).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001489359.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This variant, c.89_100del, results in the deletion of 4 amino acid(s) of the BRAF protein (p.Gly30_Ala33del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with BRAF-related conditions. ClinVar contains an entry for this variant (Variation ID: 40222). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 24, 2021

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