rs72681869
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_006939.4(SOS2):c.572C>T(p.Pro191Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P191R) has been classified as Likely benign.
Frequency
Consequence
NM_006939.4 missense
Scores
Clinical Significance
Conservation
Publications
- Noonan syndromeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- Noonan syndrome 9Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, G2P
Genome browser will be placed here
ACMG classification
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SOS2 | ENST00000216373.10 | c.572C>T | p.Pro191Leu | missense_variant | Exon 5 of 23 | 1 | NM_006939.4 | ENSP00000216373.5 | ||
SOS2 | ENST00000543680.5 | c.572C>T | p.Pro191Leu | missense_variant | Exon 5 of 22 | 1 | ENSP00000445328.1 | |||
SOS2 | ENST00000556469.5 | n.482-6033C>T | intron_variant | Intron 4 of 4 | 3 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD2 exomes AF: 0.00000402 AC: 1AN: 248898 AF XY: 0.00 show subpopulations
GnomAD4 exome Cov.: 29
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
not provided Uncertain:1
The P191L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P191L variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P191L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at