11-67428568-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003952.3(RPS6KB2):c.23A>G(p.Asp8Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
RPS6KB2
NM_003952.3 missense
NM_003952.3 missense
Scores
5
8
6
Clinical Significance
Conservation
PhyloP100: 5.54
Genes affected
RPS6KB2 (HGNC:10437): (ribosomal protein S6 kinase B2) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains a kinase catalytic domain and phosphorylates the S6 ribosomal protein and eukaryotic translation initiation factor 4B (eIF4B). Phosphorylation of S6 leads to an increase in protein synthesis and cell proliferation. [provided by RefSeq, Jan 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RPS6KB2 | NM_003952.3 | c.23A>G | p.Asp8Gly | missense_variant | 1/15 | ENST00000312629.10 | NP_003943.2 | |
RPS6KB2 | XM_047427395.1 | c.23A>G | p.Asp8Gly | missense_variant | 1/11 | XP_047283351.1 | ||
RPS6KB2 | XM_047427396.1 | c.23A>G | p.Asp8Gly | missense_variant | 1/10 | XP_047283352.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RPS6KB2 | ENST00000312629.10 | c.23A>G | p.Asp8Gly | missense_variant | 1/15 | 1 | NM_003952.3 | ENSP00000308413.5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000427 AC: 1AN: 234104Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 128882
GnomAD3 exomes
AF:
AC:
1
AN:
234104
Hom.:
AF XY:
AC XY:
0
AN XY:
128882
Gnomad AFR exome
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Gnomad SAS exome
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Gnomad FIN exome
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GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 23, 2023 | The c.23A>G (p.D8G) alteration is located in exon 1 (coding exon 1) of the RPS6KB2 gene. This alteration results from a A to G substitution at nucleotide position 23, causing the aspartic acid (D) at amino acid position 8 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Benign
DEOGEN2
Benign
T;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
.;L
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
0.99
.;D
Vest4
0.71
MutPred
Loss of stability (P = 0.0423);Loss of stability (P = 0.0423);
MVP
MPC
0.21
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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