NM_006939.4(SOS2):c.3644C>G (p.Thr1215Ser) AND Noonan syndrome 9

Clinical significance:Uncertain significance (Last evaluated: Aug 14, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001348666.1

Allele description [Variation Report for NM_006939.4(SOS2):c.3644C>G (p.Thr1215Ser)]

NM_006939.4(SOS2):c.3644C>G (p.Thr1215Ser)

Gene:
SOS2:SOS Ras/Rho guanine nucleotide exchange factor 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q21.3
Genomic location:
Preferred name:
NM_006939.4(SOS2):c.3644C>G (p.Thr1215Ser)
HGVS:
  • NC_000014.9:g.50118699G>C
  • NG_051073.1:g.117995C>G
  • NM_006939.4:c.3644C>GMANE SELECT
  • NP_008870.2:p.Thr1215Ser
  • NC_000014.8:g.50585417G>C
Protein change:
T1215S
Molecular consequence:
  • NM_006939.4:c.3644C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Noonan syndrome 9 (NS9)
Identifiers:
MONDO: MONDO:0014691; MedGen: C4225282; Orphanet: 648; OMIM: 616559

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001542975Invitaecriteria provided, single submitter
Uncertain significance
(Aug 14, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001542975.1

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

Description

This sequence change replaces threonine with serine at codon 1215 of the SOS2 protein (p.Thr1215Ser). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and serine. This variant is present in population databases (rs773877975, ExAC 0.04%). This variant has not been reported in the literature in individuals with SOS2-related conditions. 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 SOS2 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

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