rs201629454
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_006939.4(SOS2):c.2161+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000895 in 1,340,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000076 ( 0 hom. )
Consequence
SOS2
NM_006939.4 intron
NM_006939.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.74
Genes affected
SOS2 (HGNC:11188): (SOS Ras/Rho guanine nucleotide exchange factor 2) This gene encodes a regulatory protein that is involved in the positive regulation of ras proteins. Mutations in this gene are associated with Noonan Syndrome-9. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.25).
BP6
?
Variant 14-50153060-T-C is Benign according to our data. Variant chr14-50153060-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 488173.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BS2
?
High AC in GnomAdExome4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOS2 | NM_006939.4 | c.2161+10A>G | intron_variant | ENST00000216373.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOS2 | ENST00000216373.10 | c.2161+10A>G | intron_variant | 1 | NM_006939.4 | P1 | |||
SOS2 | ENST00000543680.5 | c.2062+10A>G | intron_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152176Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000867 AC: 2AN: 230564Hom.: 0 AF XY: 0.00000797 AC XY: 1AN XY: 125408
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GnomAD4 exome AF: 0.00000757 AC: 9AN: 1188436Hom.: 0 Cov.: 15 AF XY: 0.00000663 AC XY: 4AN XY: 603266
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152294Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74472
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Noonan syndrome 9 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 13, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Phosphorus, Inc. | Aug 01, 2017 | - - |
SOS2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 02, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
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DANN
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at