NM_002880.4(RAF1):c.505G>C (p.Gly169Arg) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 1, 2017
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:: RCV000576681.1

Allele description [Variation Report for NM_002880.4(RAF1):c.505G>C (p.Gly169Arg)]

NM_002880.4(RAF1):c.505G>C (p.Gly169Arg)

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.505G>C (p.Gly169Arg)

HGVS:

NC_000003.12:g.12608842C>G
NG_007467.1:g.60338G>C
NM_001354689.3:c.505G>C
NM_001354690.3:c.505G>C
NM_001354691.3:c.262G>C
NM_001354692.3:c.262G>C
NM_001354693.3:c.505G>C
NM_001354694.3:c.262G>C
NM_001354695.3:c.262G>C
NM_002880.4:c.505G>CMANE SELECT
NP_001341618.1:p.Gly169Arg
NP_001341619.1:p.Gly169Arg
NP_001341620.1:p.Gly88Arg
NP_001341621.1:p.Gly88Arg
NP_001341622.1:p.Gly169Arg
NP_001341623.1:p.Gly88Arg
NP_001341624.1:p.Gly88Arg
NP_002871.1:p.Gly169Arg
NP_002871.1:p.Gly169Arg
LRG_413t1:c.505G>C
LRG_413t2:c.505G>C
LRG_413:g.60338G>C
LRG_413p1:p.Gly169Arg
LRG_413p2:p.Gly169Arg
NC_000003.11:g.12650341C>G
NM_002880.3:c.505G>C
NR_148940.3:n.836G>C
NR_148941.3:n.836G>C
NR_148942.3:n.836G>C

Protein change:

G169R

Links:

dbSNP: rs886039607

NCBI 1000 Genomes Browser:

rs886039607

Molecular consequence:

NM_001354689.3:c.505G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354690.3:c.505G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354691.3:c.262G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354692.3:c.262G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354693.3:c.505G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354694.3:c.262G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354695.3:c.262G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002880.4:c.505G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_148940.3:n.836G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148941.3:n.836G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148942.3:n.836G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: LEOPARD syndrome 2 (LPRD2)
Identifiers:: MONDO: MONDO:0012691; MedGen: C1969056; Orphanet: 500; OMIM: 611554

Name:: Noonan syndrome 5 (NS5)
Synonyms:: RAF1 gene related Noonan syndrome
Identifiers:: MONDO: MONDO:0012690; MedGen: C1969057; Orphanet: 648; OMIM: 611553

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000678225	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 1, 2017)	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

SCV000678225

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 1, 2017)

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV000678225.1

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

Description

RAF1 NM_002880.3 exon5 p.Gly169Arg (c.505G>C):This variant has not been reported in the literature and is not present in large control databases. However, this variant is present in ClinVar, reportedly identified de novo by another laboratory (Variation ID:265535). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is highly suspicious for disease, but requires further evidence for pathogenicity. Therefore, this variant classified as likely pathogenic.

#	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: Mar 5, 2024

ClinVar

Relating variation to medicine