rs1433339408

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006939.4(SOS2):​c.3953C>G​(p.Pro1318Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

SOS2
NM_006939.4 missense

Scores

6
8
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.38
Variant links:
Genes affected
SOS2 (HGNC:11188): (SOS Ras/Rho guanine nucleotide exchange factor 2) This gene encodes a regulatory protein that is involved in the positive regulation of ras proteins. Mutations in this gene are associated with Noonan Syndrome-9. [provided by RefSeq, Jul 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27522314).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SOS2NM_006939.4 linkc.3953C>G p.Pro1318Arg missense_variant Exon 23 of 23 ENST00000216373.10 NP_008870.2 Q07890-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SOS2ENST00000216373.10 linkc.3953C>G p.Pro1318Arg missense_variant Exon 23 of 23 1 NM_006939.4 ENSP00000216373.5 Q07890-1
SOS2ENST00000543680.5 linkc.3854C>G p.Pro1285Arg missense_variant Exon 22 of 22 1 ENSP00000445328.1 Q07890-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461298
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
726976
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.18
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.53
D;.
Eigen
Pathogenic
0.75
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.85
D;D
M_CAP
Uncertain
0.095
D
MetaRNN
Benign
0.28
T;T
MetaSVM
Uncertain
0.23
D
MutationAssessor
Uncertain
2.0
M;.
PrimateAI
Benign
0.47
T
PROVEAN
Uncertain
-3.4
D;D
REVEL
Uncertain
0.60
Sift
Uncertain
0.0040
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.35
MutPred
0.25
Gain of MoRF binding (P = 0.0065);.;
MVP
0.66
MPC
0.41
ClinPred
0.93
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.36
gMVP
0.32

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-50585108; API