NM_007373.4(SHOC2):c.616A>G (p.Thr206Ala) AND RASopathy

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 13, 2023
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:: RCV001909194.3

Allele description

NM_007373.4(SHOC2):c.616A>G (p.Thr206Ala)

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.616A>G (p.Thr206Ala)

HGVS:

NC_000010.11:g.110964974A>G
NG_028922.1:g.50432A>G
NM_001269039.3:c.616A>G
NM_001324336.2:c.616A>G
NM_001324337.2:c.616A>G
NM_007373.4:c.616A>GMANE SELECT
NP_001255968.1:p.Thr206Ala
NP_001311265.1:p.Thr206Ala
NP_001311266.1:p.Thr206Ala
NP_031399.2:p.Thr206Ala
LRG_753t1:c.616A>G
LRG_753:g.50432A>G
NC_000010.10:g.112724732A>G
NM_007373.3:c.616A>G

Protein change:

T206A

Links:

dbSNP: rs370388274

NCBI 1000 Genomes Browser:

rs370388274

Molecular consequence:

NM_001269039.3:c.616A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001324336.2:c.616A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001324337.2:c.616A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_007373.4:c.616A>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002168231	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 13, 2023)	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

SCV002168231

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 13, 2023)

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

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002168231.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SHOC2 protein function. ClinVar contains an entry for this variant (Variation ID: 1403719). This variant has not been reported in the literature in individuals affected with SHOC2-related conditions. This variant is present in population databases (rs370388274, gnomAD 0.003%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 206 of the SHOC2 protein (p.Thr206Ala).

#	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: May 1, 2024

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