rs200368064
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2
The NM_006939.4(SOS2):c.1198G>A(p.Asp400Asn) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000048 in 1,604,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000047 ( 0 hom. )
Consequence
SOS2
NM_006939.4 missense, splice_region
NM_006939.4 missense, splice_region
Scores
1
7
11
Splicing: ADA: 0.9783
1
1
Clinical Significance
Conservation
PhyloP100: 7.79
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP6
?
Variant 14-50160085-C-T is Benign according to our data. Variant chr14-50160085-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 542405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOS2 | NM_006939.4 | c.1198G>A | p.Asp400Asn | missense_variant, splice_region_variant | 10/23 | ENST00000216373.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOS2 | ENST00000216373.10 | c.1198G>A | p.Asp400Asn | missense_variant, splice_region_variant | 10/23 | 1 | NM_006939.4 | P1 | |
SOS2 | ENST00000543680.5 | c.1099G>A | p.Asp367Asn | missense_variant, splice_region_variant | 9/22 | 1 | |||
SOS2 | ENST00000555794.2 | c.313G>A | p.Asp105Asn | missense_variant, splice_region_variant | 4/6 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152130Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000864 AC: 21AN: 243180Hom.: 0 AF XY: 0.0000984 AC XY: 13AN XY: 132088
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GnomAD4 exome AF: 0.0000468 AC: 68AN: 1452750Hom.: 0 Cov.: 32 AF XY: 0.0000526 AC XY: 38AN XY: 722284
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GnomAD4 genome ? AF: 0.0000592 AC: 9AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74318
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Noonan syndrome 9 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 24, 2023 | - - |
Noonan syndrome and Noonan-related syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Apr 01, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
B;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at