NM_002880.4(RAF1):c.1706_1712dup (p.Ser571delinsArgSerTer) AND RASopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 13, 2019
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:: RCV001046694.6

Allele description [Variation Report for NM_002880.4(RAF1):c.1706_1712dup (p.Ser571delinsArgSerTer)]

NM_002880.4(RAF1):c.1706_1712dup (p.Ser571delinsArgSerTer)

Gene:

RAF1:Raf-1 proto-oncogene, serine/threonine kinase [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

3p25.2

Genomic location:

Preferred name:

NM_002880.4(RAF1):c.1706_1712dup (p.Ser571delinsArgSerTer)

HGVS:

NC_000003.12:g.12584940_12584946dup
NG_007467.1:g.84236_84242dup
NM_001354689.3:c.1766_1772dup
NM_001354690.3:c.1706_1712dup
NM_001354691.3:c.1463_1469dup
NM_001354692.3:c.1463_1469dup
NM_001354693.3:c.1607_1613dup
NM_001354694.3:c.1523_1529dup
NM_001354695.3:c.1364_1370dup
NM_002880.4:c.1706_1712dupMANE SELECT
NP_001341618.1:p.Ser591delinsArgSerTer
NP_001341619.1:p.Ser571delinsArgSerTer
NP_001341620.1:p.Ser490delinsArgSerTer
NP_001341621.1:p.Ser490delinsArgSerTer
NP_001341622.1:p.Ser538delinsArgSerTer
NP_001341623.1:p.Ser510delinsArgSerTer
NP_001341624.1:p.Ser457delinsArgSerTer
NP_002871.1:p.Ser571delinsArgSerTer
NP_002871.1:p.Ser571delinsArgSerTer
LRG_413t1:c.1706_1712dup
LRG_413t2:c.1766_1772dup
LRG_413:g.84236_84242dup
LRG_413p1:p.Ser571delinsArgSerTer
LRG_413p2:p.Ser591delinsArgSerTer
NC_000003.11:g.12626436_12626437insCTAAGAT
NC_000003.11:g.12626439_12626445dup
NM_002880.3:c.1706_1712dup
NR_148940.3:n.2150_2156dup
NR_148941.3:n.2096_2102dup
NR_148942.3:n.2035_2041dup

Links:

dbSNP: rs2058277475

NCBI 1000 Genomes Browser:

rs2058277475

Molecular consequence:

NR_148940.3:n.2150_2156dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148941.3:n.2096_2102dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148942.3:n.2035_2041dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001354689.3:c.1766_1772dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001354690.3:c.1706_1712dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001354691.3:c.1463_1469dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001354692.3:c.1463_1469dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001354693.3:c.1607_1613dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001354694.3:c.1523_1529dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001354695.3:c.1364_1370dup - nonsense - [Sequence Ontology: SO:0001587]
NM_002880.4:c.1706_1712dup - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: RASopathy
Synonyms:: rasopathies; Noonan spectrum disorder
Identifiers:: MONDO: MONDO:0021060; MedGen: C5555857

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001210608	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 13, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001210608

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 13, 2019)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001210608.5

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

Description

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. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in RAF1 cause disease. This variant has not been reported in the literature in individuals with RAF1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser571Argfs*3) in the RAF1 gene. It is expected to result in an absent or disrupted protein product.

#	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		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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