chr14-50118399-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_006939.4(SOS2):c.3944C>T(p.Ser1315Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000167 in 1,614,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S1315S) has been classified as Likely benign.
Frequency
Consequence
NM_006939.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOS2 | NM_006939.4 | c.3944C>T | p.Ser1315Leu | missense_variant | 23/23 | ENST00000216373.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOS2 | ENST00000216373.10 | c.3944C>T | p.Ser1315Leu | missense_variant | 23/23 | 1 | NM_006939.4 | P1 | |
SOS2 | ENST00000543680.5 | c.3845C>T | p.Ser1282Leu | missense_variant | 22/22 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251486Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135916
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461828Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 727222
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74344
ClinVar
Submissions by phenotype
Noonan syndrome 9 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 02, 2023 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 09, 2022 | The p.S1315L variant (also known as c.3944C>T), located in coding exon 23 of the SOS2 gene, results from a C to T substitution at nucleotide position 3944. The serine at codon 1315 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at