NM_002880.4(RAF1):c.1669-19_1672dup AND RASopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 17, 2021
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:: RCV001866295.5

Allele description [Variation Report for NM_002880.4(RAF1):c.1669-19_1672dup]

NM_002880.4(RAF1):c.1669-19_1672dup

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.1669-19_1672dup

HGVS:

NC_000003.12:g.12584981_12585003dup
NG_007467.1:g.84180_84202dup
NM_001354689.3:c.1729-19_1732dup
NM_001354690.3:c.1669-19_1672dup
NM_001354691.3:c.1426-19_1429dup
NM_001354692.3:c.1426-19_1429dup
NM_001354693.3:c.1570-19_1573dup
NM_001354694.3:c.1486-19_1489dup
NM_001354695.3:c.1327-19_1330dup
NM_002880.4:c.1669-19_1672dupMANE SELECT
LRG_413t2:c.1729-19_1732dup
LRG_413:g.84180_84202dup
NC_000003.11:g.12626476_12626477insTGATCTAAGGGAAAGAAAACAGC
NC_000003.11:g.12626480_12626502dup

Links:

dbSNP: rs2125320099

NCBI 1000 Genomes Browser:

rs2125320099

Molecular consequence:

NM_001354689.3:c.1729-19_1732dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354690.3:c.1669-19_1672dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354691.3:c.1426-19_1429dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354692.3:c.1426-19_1429dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354693.3:c.1570-19_1573dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354694.3:c.1486-19_1489dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354695.3:c.1327-19_1330dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_002880.4:c.1669-19_1672dup - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

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

Recent activity

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Saccharomyces cerevisiae isolate yazhong 16 internal transcribed spacer 1, parti...
Saccharomyces cerevisiae isolate yazhong 16 internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA gene and internal transcribed spacer 2, complete sequence; and large subunit ribosomal RNA gene, partial sequence
gi|1179788147|gb|KX434760.1|

Nucleotide
Caspase Activation in Cancer Therapy - Madame Curie Bioscience Database
Caspase Activation in Cancer Therapy - Madame Curie Bioscience Database
Tfb2m transcription factor B2, mitochondrial [Rattus norvegicus]
Tfb2m transcription factor B2, mitochondrial [Rattus norvegicus]
Gene ID:289307

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002120149	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 17, 2021)	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

SCV002120149

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 17, 2021)

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, SCV002120149.2

#	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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with RAF1-related conditions. This variant is also known as c.1669-19_1672dup (p.Ile558Serfs*32). This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 15 of the RAF1 gene. It does not directly change the encoded amino acid sequence of the RAF1 protein.

#	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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