14-50118408-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_006939.4(SOS2):c.3935G>A(p.Arg1312Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,613,952 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1312W) has been classified as Uncertain significance.
Frequency
Consequence
NM_006939.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOS2 | NM_006939.4 | c.3935G>A | p.Arg1312Gln | missense_variant | 23/23 | ENST00000216373.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOS2 | ENST00000216373.10 | c.3935G>A | p.Arg1312Gln | missense_variant | 23/23 | 1 | NM_006939.4 | P1 | |
SOS2 | ENST00000543680.5 | c.3836G>A | p.Arg1279Gln | missense_variant | 22/22 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152074Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251490Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135916
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461878Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727242
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152074Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74278
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 22, 2023 | The p.R1312Q variant (also known as c.3935G>A), located in coding exon 23 of the SOS2 gene, results from a G to A substitution at nucleotide position 3935. The arginine at codon 1312 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Noonan syndrome 9 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at