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:

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000062456	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Dec 3, 2014)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19684605, 20882035, 23918763, 24033266
SCV000264222	Blueprint Genetics	criteria provided, single submitter (Variant Classification)	Pathogenic (Jan 26, 2015)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 19684605, 22528146, 23918763, 24458587, 24458596 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000062456

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Dec 3, 2014)

germline

clinical testing

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

SCV000264222

Blueprint Genetics

criteria provided, single submitter

(Variant Classification)

Pathogenic
(Jan 26, 2015)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	30	29	not provided	not provided	not provided	clinical testing

Citations

PubMed

Nothing to display

See all PubMed Citations (7)

Details of each submission

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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	30	not provided	not provided	clinical 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		30	not provided	29	not provided

From Blueprint Genetics, SCV000264222.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (5)

#	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		2	not provided	not provided	not provided

Last Updated: Nov 18, 2024

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