NM_006939.4(SOS2):c.3952C>T (p.Pro1318Ser) AND not specified

Clinical significance:Likely benign (Last evaluated: Mar 23, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001175493.1

Allele description [Variation Report for NM_006939.4(SOS2):c.3952C>T (p.Pro1318Ser)]

NM_006939.4(SOS2):c.3952C>T (p.Pro1318Ser)

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.3952C>T (p.Pro1318Ser)
HGVS:
  • NC_000014.9:g.50118391G>A
  • NG_051073.1:g.118303C>T
  • NM_006939.4:c.3952C>TMANE SELECT
  • NP_008870.2:p.Pro1318Ser
  • NC_000014.8:g.50585109G>A
  • NM_006939.2:c.3952C>T
  • NM_006939.3:c.3952C>T
Protein change:
P1318S
Links:
dbSNP: rs140995728
NCBI 1000 Genomes Browser:
rs140995728
Molecular consequence:
  • NM_006939.4:c.3952C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001339086Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely benign
(Mar 23, 2020)
germlineclinical testing

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Activating Mutations Affecting the Dbl Homology Domain of SOS2 Cause Noonan Syndrome.

Cordeddu V, Yin JC, Gunnarsson C, Virtanen C, Drunat S, Lepri F, De Luca A, Rossi C, Ciolfi A, Pugh TJ, Bruselles A, Priest JR, Pennacchio LA, Lu Z, Danesh A, Quevedo R, Hamid A, Martinelli S, Pantaleoni F, Gnazzo M, Daniele P, Lissewski C, et al.

Hum Mutat. 2015 Nov;36(11):1080-7. doi: 10.1002/humu.22834. Epub 2015 Aug 3.

PubMed [citation]
PMID:
26173643
PMCID:
PMC4604019

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001339086.1

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

Description

Variant summary: SOS2 c.3952C>T (p.Pro1318Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0005 in 251440 control chromosomes, predominantly at a frequency of 0.00095 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 380 fold of the estimated maximal expected allele frequency for a pathogenic variant in SOS2 causing Noonan Syndrome and Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.3952C>T has been reported in the literature in individuals affected with Noonan Syndrome and Related Conditions, without strong evidence for causality (Cordeddu_2015). This report does not provide unequivocal conclusions about association of the variant with Noonan Syndrome and Related Conditions. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

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

Last Updated: Oct 8, 2021

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