rs775682587
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_006939.4(SOS2):āc.2520A>Gā(p.Ala840=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,601,986 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 (ā ā ). Synonymous variant affecting the same amino acid position (i.e. A840A) has been classified as Likely benign.
Frequency
Consequence
NM_006939.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOS2 | NM_006939.4 | c.2520A>G | p.Ala840= | synonymous_variant | 16/23 | ENST00000216373.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOS2 | ENST00000216373.10 | c.2520A>G | p.Ala840= | synonymous_variant | 16/23 | 1 | NM_006939.4 | P1 | |
SOS2 | ENST00000543680.5 | c.2421A>G | p.Ala807= | synonymous_variant | 15/22 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152190Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000888 AC: 211AN: 237700Hom.: 0 AF XY: 0.000683 AC XY: 88AN XY: 128878
GnomAD4 exome AF: 0.000157 AC: 227AN: 1449796Hom.: 0 Cov.: 31 AF XY: 0.000130 AC XY: 94AN XY: 720994
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74348
ClinVar
Submissions by phenotype
Noonan syndrome 9 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 10, 2024 | - - |
not provided Benign:1
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.2520A>G (p.Ala840Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect binding of multiple ESE sites. These predictions have not been confirmed by functional studies. This variant was found in 105/119170 control chromosomes from ExAC, predominantly observed in the Latino subpopulation at a frequency of 0.009083 (105/11560). This frequency is about 3633 times the estimated maximal expected allele frequency of a pathogenic SOS2 variant (0.0000025), suggesting this is likely a benign polymorphism found primarily in the populations of Latino origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Taken together, this variant is classified as Benign. - |
SOS2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 30, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 29, 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at