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NM_007373.4(SHOC2):c.4A>G (p.Ser2Gly) AND Noonan syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Jan 26, 2015
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:
RCV000208379.13

Allele description [Variation Report for NM_007373.4(SHOC2):c.4A>G (p.Ser2Gly)]

NM_007373.4(SHOC2):c.4A>G (p.Ser2Gly)

Gene:
SHOC2:SHOC2 leucine rich repeat scaffold protein [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q25.2
Genomic location:
Preferred name:
NM_007373.4(SHOC2):c.4A>G (p.Ser2Gly)
Other names:
p.S2G:AGT>GGT; NM_007373.3(SHOC2):c.4A>G
HGVS:
  • NC_000010.11:g.110964362A>G
  • NG_028922.1:g.49820A>G
  • NM_001269039.3:c.4A>G
  • NM_001324336.2:c.4A>G
  • NM_001324337.2:c.4A>G
  • NM_007373.4:c.4A>GMANE SELECT
  • NP_001255968.1:p.Ser2Gly
  • NP_001311265.1:p.Ser2Gly
  • NP_001311266.1:p.Ser2Gly
  • NP_001311266.1:p.Ser2Gly
  • NP_031399.2:p.Ser2Gly
  • NP_031399.2:p.Ser2Gly
  • LRG_753t1:c.4A>G
  • LRG_753:g.49820A>G
  • LRG_753p1:p.Ser2Gly
  • NC_000010.10:g.112724120A>G
  • NM_001269039.1:c.4A>G
  • NM_001269039.2:c.4A>G
  • NM_001324337.1:c.4A>G
  • NM_007373.3:c.4A>G
  • Q9UQ13:p.Ser2Gly
  • c.4A>G
Protein change:
S2G; SER2GLY
Links:
UniProtKB: Q9UQ13#VAR_060199; OMIM: 602775.0001; dbSNP: rs267607048
NCBI 1000 Genomes Browser:
rs267607048
Molecular consequence:
  • NM_001269039.3:c.4A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001324336.2:c.4A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001324337.2:c.4A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007373.4:c.4A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
29

Condition(s)

Name:
Noonan syndrome (NS)
Synonyms:
Noonan's syndrome; Pseudo-Turner syndrome
Identifiers:
MONDO: MONDO:0018997; MeSH: D009634; MedGen: C0028326; OMIM: PS163950

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000062456Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(Dec 3, 2014) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV000264222Blueprint Genetics
criteria provided, single submitter

(Variant Classification)		Pathogenic
(Jan 26, 2015) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes2not providednot providednot providednot providedclinical testing
not providedgermlinenot provided3029not providednot providednot providedclinical testing

Citations

PubMed

Mutation analysis of the SHOC2 gene in Noonan-like syndrome and in hematologic malignancies.

Komatsuzaki S, Aoki Y, Niihori T, Okamoto N, Hennekam RC, Hopman S, Ohashi H, Mizuno S, Watanabe Y, Kamasaki H, Kondo I, Moriyama N, Kurosawa K, Kawame H, Okuyama R, Imaizumi M, Rikiishi T, Tsuchiya S, Kure S, Matsubara Y.

J Hum Genet. 2010 Dec;55(12):801-9. doi: 10.1038/jhg.2010.116. Epub 2010 Sep 30.

PubMed [citation]
PMID:
20882035

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020
See all PubMed Citations (7)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000062456.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided30not providednot providedclinical testing PubMed (4)

Description

The p.Ser2Gly variant in SHOC2 is an established pathogenic variant for Noonan s yndrome with loose anagen hair. The variant was identified in >40 affected indiv iduals across multiple studies and in multiple cases was shown to be de novo (Co rdeddu 2009, Komatsuzaki 2010, Gripp 2013, LMM data). It has not been identified large population studies. In vitro functional studies provide some evidence tha t the p.Ser2Gly variant impacts protein function (Cordeddu 2009). In summary, th is variant meets our criteria to be classified as pathogenic for Noonan syndrome in an autosomal dominant manner.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided30not provided29not provided

From Blueprint Genetics, SCV000264222.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (5)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided2not providednot providednot provided

Last Updated: Nov 3, 2024