rs542617984
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2
The NM_006939.4(SOS2):c.837C>T(p.Ser279=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000657 in 1,613,926 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000068 ( 0 hom. )
Consequence
SOS2
NM_006939.4 synonymous
NM_006939.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.38
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
?
Variant 14-50182484-G-A is Benign according to our data. Variant chr14-50182484-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 542406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOS2 | NM_006939.4 | c.837C>T | p.Ser279= | synonymous_variant | 6/23 | ENST00000216373.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOS2 | ENST00000216373.10 | c.837C>T | p.Ser279= | synonymous_variant | 6/23 | 1 | NM_006939.4 | P1 | |
SOS2 | ENST00000543680.5 | c.837C>T | p.Ser279= | synonymous_variant | 6/22 | 1 | |||
SOS2 | ENST00000556469.5 | n.604C>T | non_coding_transcript_exon_variant | 5/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152130Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251178Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135748
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GnomAD4 exome AF: 0.0000677 AC: 99AN: 1461678Hom.: 0 Cov.: 30 AF XY: 0.0000688 AC XY: 50AN XY: 727128
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152248Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74442
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Noonan syndrome 9 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2022 | SOS2: BP4, BP7 - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 17, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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