rs17122201
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_006939.4(SOS2):c.1448G>A(p.Ser483Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00492 in 1,614,066 control chromosomes in the GnomAD database, including 284 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_006939.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOS2 | NM_006939.4 | c.1448G>A | p.Ser483Asn | missense_variant | 10/23 | ENST00000216373.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOS2 | ENST00000216373.10 | c.1448G>A | p.Ser483Asn | missense_variant | 10/23 | 1 | NM_006939.4 | P1 | |
SOS2 | ENST00000543680.5 | c.1349G>A | p.Ser450Asn | missense_variant | 9/22 | 1 | |||
SOS2 | ENST00000555794.2 | c.563G>A | p.Ser188Asn | missense_variant | 4/6 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0243 AC: 3695AN: 152098Hom.: 143 Cov.: 32
GnomAD3 exomes AF: 0.00707 AC: 1777AN: 251358Hom.: 67 AF XY: 0.00526 AC XY: 714AN XY: 135848
GnomAD4 exome AF: 0.00290 AC: 4237AN: 1461850Hom.: 140 Cov.: 32 AF XY: 0.00254 AC XY: 1846AN XY: 727226
GnomAD4 genome ? AF: 0.0244 AC: 3707AN: 152216Hom.: 144 Cov.: 32 AF XY: 0.0232 AC XY: 1729AN XY: 74418
ClinVar
Submissions by phenotype
Noonan syndrome 9 Benign:3
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 14, 2023 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 28, 2016 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 12, 2017 | Variant summary: The SOS2 c.1448G>A (p.Ser483Asn) variant involves the alteration of a non-conserved nucleotide, resulting in a missense substitution. The variant lies within the Pleckstrin homology domain (InterPro) and 4/4 in silico tools predict a benign outcome for this variant. This variant was found in the large control database ExAC at a frequency of 0.0084862 in all populations (1030/121374 control chromosomes [39 homozygotes]), but was observed most commonly in the African subpopulation at a frequency of 0.087794 (912/10388 [38 homozygotes]). This frequency is about 35118 times the estimated maximal expected allele frequency of a pathogenic SOS2 variant (0.0000025), providing strong evidence that this is likely a benign polymorphism found primarily in the populations of African origin. One publication has reported the variant in 6 individuals diagnosed with RASopathies or Noonan syndrome. However, co-segregation data was not provided and the authors classified the variant as a polymorphism (Cordeddu_HM_2015). In addition, one clinical diagnostic laboratories classified this variant as benign. Taken together, this variant is classified as benign. - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 04, 2018 | This alteration is classified as 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. - |
Noonan syndrome and Noonan-related syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Mar 18, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at