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NM_006939.4(SOS2):c.800T>G (p.Met267Arg)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
6 (Most recent: Aug 20, 2021)
Last evaluated:
Oct 19, 2020
Accession:
VCV000577079.10
Variation ID:
577079
Description:
single nucleotide variant
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NM_006939.4(SOS2):c.800T>G (p.Met267Arg)

Allele ID
566487
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
14q21.3
Genomic location
14: 50182521 (GRCh38) GRCh38 UCSC
14: 50649239 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000014.8:g.50649239A>C
NC_000014.9:g.50182521A>C
NG_051073.1:g.54173T>G
NM_006939.4:c.800T>G MANE Select NP_008870.2:p.Met267Arg missense
Protein change
M267R
Other names
-
Canonical SPDI
NC_000014.9:50182520:A:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
dbSNP: rs797045167
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 3 criteria provided, multiple submitters, no conflicts Jul 2, 2020 RCV000699741.4
Likely pathogenic 1 criteria provided, single submitter Oct 19, 2020 RCV001264473.1
Pathogenic 1 criteria provided, single submitter Aug 5, 2020 RCV001575734.3
Pathogenic 1 no assertion criteria provided - RCV001251214.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
SOS2 - - GRCh38
GRCh37
467 483

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Aug 20, 2018)
criteria provided, single submitter
Method: clinical testing
Noonan syndrome 9
Allele origin: germline
Invitae
Accession: SCV000828465.2
Submitted: (Mar 28, 2019)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change replaces methionine with arginine at codon 267 of the SOS2 protein (p.Met267Arg). The methionine residue is highly conserved and there is a … (more)
Pathogenic
(Jul 02, 2020)
criteria provided, single submitter
Method: clinical testing
Noonan syndrome 9
(Autosomal dominant inheritance)
Allele origin: de novo
Department of Human Genetics, University Hospital Magdeburg
Accession: SCV001426179.1
Submitted: (Jul 02, 2020)
Evidence details
Publications
PubMed (1)
Comment:
This variant has been previously reported as pathogenic including well-established functional studies (PS1 and PS3). It is absent from gnomAD (PM2). Variants at the analogous … (more)
Likely pathogenic
(Oct 19, 2020)
criteria provided, single submitter
Method: clinical testing
Rasopathy
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001442647.1
Submitted: (Nov 10, 2020)
Evidence details
Publications
PubMed (5)
Comment:
Variant summary: SOS2 c.800T>G (p.Met267Arg) results in a non-conservative amino acid change located in the Dbl homology (DH) domain (IPR000219) of the encoded protein sequence. … (more)
Pathogenic
(Mar 23, 2020)
criteria provided, single submitter
Method: clinical testing
Noonan syndrome 9
Allele origin: unknown
Centre for Mendelian Genomics,University Medical Centre Ljubljana
Accession: SCV001366232.2
Submitted: (Nov 24, 2020)
Evidence details
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS3,PM2,PM5,PP3.
Pathogenic
(Aug 05, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001802788.1
Submitted: (Aug 20, 2021)
Evidence details
Comment:
Published functional studies demonstrate variant promotes enhanced phosphorylation of extracellular signal-regulated kinase (ERK) compared to wild type protein (Cordeddu et al., 2015); Not observed in … (more)
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
Noonan syndrome
Allele origin: de novo
Service de Génétique Moléculaire,Hôpital Robert Debré
Accession: SCV001426700.1
Submitted: (Aug 04, 2020)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
A report on a girl of Noonan syndrome 9 presenting with bilateral lower limbs lymphedema. Ding Y Chinese medical journal 2019 PMID: 30707178
Dermatological manifestations in Noonan syndrome: a prospective multicentric study of 129 patients positive for mutation. Bessis D The British journal of dermatology 2019 PMID: 30417923
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Expansion of the RASopathies. Tidyman WE Current genetic medicine reports 2016 PMID: 27942422
Activating Mutations Affecting the Dbl Homology Domain of SOS2 Cause Noonan Syndrome. Cordeddu V Human mutation 2015 PMID: 26173643
Rare variants in SOS2 and LZTR1 are associated with Noonan syndrome. Yamamoto GL Journal of medical genetics 2015 PMID: 25795793

Text-mined citations for rs797045167...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 29, 2021