NM_002880.4(RAF1):c.1688G>A (p.Arg563Gln) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 18, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000680316.3

Allele description [Variation Report for NM_002880.4(RAF1):c.1688G>A (p.Arg563Gln)]

NM_002880.4(RAF1):c.1688G>A (p.Arg563Gln)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.2

Genomic location:

Preferred name:

NM_002880.4(RAF1):c.1688G>A (p.Arg563Gln)

HGVS:

NC_000003.12:g.12584962C>T
NG_007467.1:g.84218G>A
NM_001354689.3:c.1748G>A
NM_001354690.3:c.1688G>A
NM_001354691.3:c.1445G>A
NM_001354692.3:c.1445G>A
NM_001354693.3:c.1589G>A
NM_001354694.3:c.1505G>A
NM_001354695.3:c.1346G>A
NM_002880.4:c.1688G>AMANE SELECT
NP_001341618.1:p.Arg583Gln
NP_001341619.1:p.Arg563Gln
NP_001341620.1:p.Arg482Gln
NP_001341621.1:p.Arg482Gln
NP_001341622.1:p.Arg530Gln
NP_001341623.1:p.Arg502Gln
NP_001341624.1:p.Arg449Gln
NP_002871.1:p.Arg563Gln
NP_002871.1:p.Arg563Gln
LRG_413t1:c.1688G>A
LRG_413t2:c.1748G>A
LRG_413:g.84218G>A
LRG_413p1:p.Arg563Gln
LRG_413p2:p.Arg583Gln
NC_000003.11:g.12626461C>T
NM_002880.3:c.1688G>A
NR_148940.3:n.2132G>A
NR_148941.3:n.2078G>A
NR_148942.3:n.2017G>A

Protein change:

R449Q

Links:

dbSNP: rs727504827

NCBI 1000 Genomes Browser:

rs727504827

Molecular consequence:

NM_001354689.3:c.1748G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354690.3:c.1688G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354691.3:c.1445G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354692.3:c.1445G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354693.3:c.1589G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354694.3:c.1505G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354695.3:c.1346G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002880.4:c.1688G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_148940.3:n.2132G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148941.3:n.2078G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148942.3:n.2017G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000490892	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jan 30, 2020)	germline	clinical testing	Citation Link,
SCV004562747	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Uncertain significance (Oct 18, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000490892

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jan 30, 2020)

germline

clinical testing

Citation Link,

SCV004562747

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2024)

Uncertain significance
(Oct 18, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000490892.3

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

Description

In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); Has not been previously published as pathogenic or benign to our knowledge

#	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		not provided	not provided	not provided	not provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV004562747.1

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

Description

The RAF1 c.1688G>A; p.Arg563Gln variant (rs727504827), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 179378). This variant is found in the general population with an overall allele frequency of 0.002 % (5/251250 alleles) in the Genome Aggregation Database. Computational analyses predict that this variant is deleterious (REVEL: 0.777). Due to limited information, the clinical significance of this variant is uncertain at this time.

#	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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