14-50145232-C-T
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_006939.4(SOS2):c.2605G>A(p.Val869Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,610,334 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V869A) has been classified as Uncertain significance.
Frequency
Consequence
NM_006939.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOS2 | NM_006939.4 | c.2605G>A | p.Val869Ile | missense_variant | 16/23 | ENST00000216373.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOS2 | ENST00000216373.10 | c.2605G>A | p.Val869Ile | missense_variant | 16/23 | 1 | NM_006939.4 | P1 | |
SOS2 | ENST00000543680.5 | c.2506G>A | p.Val836Ile | missense_variant | 15/22 | 1 |
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152054Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000267 AC: 67AN: 251052Hom.: 1 AF XY: 0.000236 AC XY: 32AN XY: 135718
GnomAD4 exome AF: 0.000127 AC: 185AN: 1458280Hom.: 1 Cov.: 30 AF XY: 0.000110 AC XY: 80AN XY: 725772
GnomAD4 genome AF: 0.000151 AC: 23AN: 152054Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74270
ClinVar
Submissions by phenotype
Noonan syndrome 9 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 12, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 20, 2022 | - - |
SOS2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 16, 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at