NM_006939.4(SOS2):c.2057+19T>A AND not specified

Clinical significance:Benign/Likely benign (Last evaluated: Aug 26, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000616553.2

Allele description [Variation Report for NM_006939.4(SOS2):c.2057+19T>A]

NM_006939.4(SOS2):c.2057+19T>A

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.2057+19T>A
HGVS:
  • NC_000014.9:g.50156980A>T
  • NG_051073.1:g.79714T>A
  • NM_006939.4:c.2057+19T>AMANE SELECT
  • NC_000014.8:g.50623698A>T
  • NM_006939.2:c.2057+19T>A
  • NM_006939.3:c.2057+19T>A
Links:
dbSNP: rs544924513
NCBI 1000 Genomes Browser:
rs544924513
Molecular consequence:
  • NM_006939.4:c.2057+19T>A - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000714097GeneDxcriteria provided, single submitter
Likely benign
(Apr 4, 2017)
germlineclinical testing

Citation Link,

SCV001361613Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Benign
(Aug 26, 2019)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000714097.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001361613.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Variant summary: SOS2 c.2057+19T>A alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00032 in 155274 control chromosomes (gnomAD). The observed variant frequency is approximately 128 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 benign. To our knowledge, no occurrence of c.2057+19T>A in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.

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

Last Updated: Jun 14, 2021

Support Center