NM_006939.4:c.3546_3548delTCC
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PM4_SupportingBS2
The NM_006939.4(SOS2):c.3546_3548delTCC(p.Pro1183del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000993 in 1,410,218 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000099 ( 1 hom. )
Consequence
SOS2
NM_006939.4 disruptive_inframe_deletion
NM_006939.4 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.60
Publications
0 publications found
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]
SOS2 Gene-Disease associations (from GenCC):
- 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
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_006939.4. Strenght limited to Supporting due to length of the change: 1aa.
BS2
High AC in GnomAdExome4 at 14 AD gene.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_006939.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SOS2 | NM_006939.4 | MANE Select | c.3546_3548delTCC | p.Pro1183del | disruptive_inframe_deletion | Exon 23 of 23 | NP_008870.2 | ||
| SOS2 | NM_001411020.1 | c.3447_3449delTCC | p.Pro1150del | disruptive_inframe_deletion | Exon 22 of 22 | NP_001397949.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SOS2 | ENST00000216373.10 | TSL:1 MANE Select | c.3546_3548delTCC | p.Pro1183del | disruptive_inframe_deletion | Exon 23 of 23 | ENSP00000216373.5 | ||
| SOS2 | ENST00000543680.5 | TSL:1 | c.3447_3449delTCC | p.Pro1150del | disruptive_inframe_deletion | Exon 22 of 22 | ENSP00000445328.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
30
GnomAD2 exomes AF: 0.0000173 AC: 4AN: 230798 AF XY: 0.0000159 show subpopulations
GnomAD2 exomes
AF:
AC:
4
AN:
230798
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000993 AC: 14AN: 1410218Hom.: 1 AF XY: 0.0000129 AC XY: 9AN XY: 697792 show subpopulations
GnomAD4 exome
AF:
AC:
14
AN:
1410218
Hom.:
AF XY:
AC XY:
9
AN XY:
697792
show subpopulations
African (AFR)
AF:
AC:
0
AN:
32226
American (AMR)
AF:
AC:
0
AN:
40592
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24602
East Asian (EAS)
AF:
AC:
0
AN:
38316
South Asian (SAS)
AF:
AC:
12
AN:
80546
European-Finnish (FIN)
AF:
AC:
1
AN:
51842
Middle Eastern (MID)
AF:
AC:
0
AN:
5540
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1078820
Other (OTH)
AF:
AC:
0
AN:
57734
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
1
2
4
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6
0.00
0.20
0.40
0.60
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0.95
Allele balance
Age Distribution
Exome Het
Exome Hom
Variant carriers
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4
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10
<30
30-35
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
30
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Noonan syndrome 9 Uncertain:1
Feb 24, 2020
Revvity Omics, Revvity
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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