NM_002880.4(RAF1):c.1941C>T (p.Val647=) AND RASopathy

Germline classification:: Benign (3 submissions)
Last evaluated:: Apr 18, 2017
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV000149840.25

Allele description [Variation Report for NM_002880.4(RAF1):c.1941C>T (p.Val647=)]

NM_002880.4(RAF1):c.1941C>T (p.Val647=)

Genes:

MKRN2:makorin ring finger protein 2 [Gene - OMIM - HGNC]
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.1941C>T (p.Val647=)

Other names:

p.V647V:GTC>GTT; NM_002880.3(RAF1):c.1941C>T

HGVS:

NC_000003.12:g.12584520G>A
NG_007467.1:g.84660C>T
NM_001354689.3:c.2001C>T
NM_001354690.3:c.1941C>T
NM_001354691.3:c.1698C>T
NM_001354692.3:c.1698C>T
NM_001354693.3:c.1842C>T
NM_001354694.3:c.1758C>T
NM_001354695.3:c.1599C>T
NM_002880.4:c.1941C>TMANE SELECT
NP_001341618.1:p.Val667=
NP_001341619.1:p.Val647=
NP_001341620.1:p.Val566=
NP_001341621.1:p.Val566=
NP_001341622.1:p.Val614=
NP_001341623.1:p.Val586=
NP_001341624.1:p.Val533=
NP_002871.1:p.Val647=
NP_002871.1:p.Val647=
LRG_413t1:c.1941C>T
LRG_413t2:c.2001C>T
LRG_413:g.84660C>T
LRG_413p1:p.Val647=
LRG_413p2:p.Val667=
NC_000003.11:g.12626019G>A
NM_002880.2:c.1941C>T
NM_002880.3:c.1941C>T
NR_148940.3:n.2385C>T
NR_148941.3:n.2331C>T
NR_148942.3:n.2270C>T
c.1941C>T
p.Val647Val

Links:

dbSNP: rs3730297

NCBI 1000 Genomes Browser:

rs3730297

Molecular consequence:

NR_148940.3:n.2385C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148941.3:n.2331C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148942.3:n.2270C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001354689.3:c.2001C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001354690.3:c.1941C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001354691.3:c.1698C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001354692.3:c.1698C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001354693.3:c.1842C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001354694.3:c.1758C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001354695.3:c.1599C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_002880.4:c.1941C>T - synonymous variant - [Sequence Ontology: SO:0001819]

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
SCV000196684	Baylor Genetics	no assertion criteria provided	Benign	unknown	clinical testing
SCV000287741	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Feb 1, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000616477	ClinGen RASopathy Variant Curation Expert Panel	reviewed by expert panel (ClinGen RASopathy ACMG Specifications v1)	Benign (Apr 18, 2017)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000196684

Baylor Genetics

no assertion criteria provided

Benign

unknown

clinical testing

SCV000287741

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Feb 1, 2024)

germline

clinical testing

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

SCV000616477

ClinGen RASopathy Variant Curation Expert Panel

reviewed by expert panel

(ClinGen RASopathy ACMG Specifications v1)

Benign
(Apr 18, 2017)

germline

curation

Citation Link

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, curation
not provided	unknown	yes	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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Baylor Genetics, SCV000196684.1

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

Description

Variant classified using ACMG guidelines

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV000287741.10

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

#	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

From ClinGen RASopathy Variant Curation Expert Panel, SCV000616477.4

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

Description

The filtering allele frequency of the c.1941C>T (p.Val647=) variant in the RAF1 gene is 1.04% (738/66732) of European chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581)

#	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: Apr 20, 2024

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