NM_002880.4(RAF1):c.1457A>G (p.Asp486Gly) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 27, 2025
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:: RCV000434022.10

Allele description [Variation Report for NM_002880.4(RAF1):c.1457A>G (p.Asp486Gly)]

NM_002880.4(RAF1):c.1457A>G (p.Asp486Gly)

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.1457A>G (p.Asp486Gly)

HGVS:

NC_000003.12:g.12585760T>C
NG_007467.1:g.83420A>G
NM_001354689.3:c.1517A>G
NM_001354690.3:c.1457A>G
NM_001354691.3:c.1214A>G
NM_001354692.3:c.1214A>G
NM_001354693.3:c.1358A>G
NM_001354694.3:c.1274A>G
NM_001354695.3:c.1115A>G
NM_002880.4:c.1457A>GMANE SELECT
NP_001341618.1:p.Asp506Gly
NP_001341619.1:p.Asp486Gly
NP_001341620.1:p.Asp405Gly
NP_001341621.1:p.Asp405Gly
NP_001341622.1:p.Asp453Gly
NP_001341623.1:p.Asp425Gly
NP_001341624.1:p.Asp372Gly
NP_002871.1:p.Asp486Gly
NP_002871.1:p.Asp486Gly
LRG_413t1:c.1457A>G
LRG_413t2:c.1517A>G
LRG_413:g.83420A>G
LRG_413p1:p.Asp486Gly
LRG_413p2:p.Asp506Gly
NC_000003.11:g.12627259T>C
NM_002880.3:c.1457A>G
NR_148940.3:n.1901A>G
NR_148941.3:n.1847A>G
NR_148942.3:n.1786A>G
P04049:p.Asp486Gly
c.1457A>G

Protein change:

D372G

Links:

UniProtKB: P04049#VAR_037816; dbSNP: rs397516815

NCBI 1000 Genomes Browser:

rs397516815

Molecular consequence:

NM_001354689.3:c.1517A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354690.3:c.1457A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354691.3:c.1214A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354692.3:c.1214A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354693.3:c.1358A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354694.3:c.1274A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354695.3:c.1115A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002880.4:c.1457A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_148940.3:n.1901A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148941.3:n.1847A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148942.3:n.1786A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000514364	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Feb 27, 2025)	germline	clinical testing	Citation Link,
SCV000706413	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL ClinVar v180209 classification definitions)	Pathogenic (Jul 3, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000514364

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Feb 27, 2025)

germline

clinical testing

Citation Link,

SCV000706413

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL ClinVar v180209 classification definitions)

Pathogenic
(Jul 3, 2018)

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	2	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000514364.9

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23885229, 23093928, 25862627, 24803665, 17603483, 35979676, 32059087, 24957944, 9689060, 15520807, 17603482, 29493581, 19020799)

#	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 Eurofins Ntd Llc (ga), SCV000706413.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	not provided

#	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		2	not provided	not provided	not provided

Last Updated: Apr 13, 2025

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