rs35363135

Positions:

• chr11-67428578-G-A
• chr11-67428578-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_003952.3(RPS6KB2):​c.33G>A​(p.Thr11=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 1,611,052 control chromosomes in the GnomAD database, including 6,533 homozygotes. 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: 𝑓 0.12 (3526 hom., cov: 32)
  • Exomes 𝑓: 0.013 (3007 hom.)
• Consequence: RPS6KB2 NM_003952.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP7: Synonymous conserved (PhyloP=-0.312 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KB2	NM_003952.3	c.33G>A	p.Thr11=	synonymous_variant	1/15	ENST00000312629.10
RPS6KB2	XM_047427395.1	c.33G>A	p.Thr11=	synonymous_variant	1/11
RPS6KB2	XM_047427396.1	c.33G>A	p.Thr11=	synonymous_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KB2	ENST00000312629.10	c.33G>A	p.Thr11=	synonymous_variant	1/15	1	NM_003952.3	P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18041 AN: 152136 Hom.: 3525 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0516

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.00245

Gnomad OTH AF: 0.0870

GnomAD3 exomes AF: 0.0291 AC: 6829 AN: 234914 Hom.: 1187 AF XY: 0.0223 AC XY: 2883 AN XY: 129258

Gnomad AFR exome AF: 0.407

Gnomad AMR exome AF: 0.0215

Gnomad ASJ exome AF: 0.00774

Gnomad EAS exome AF: 0.0000566

Gnomad SAS exome AF: 0.000560

Gnomad FIN exome AF: 0.000146

Gnomad NFE exome AF: 0.00189

Gnomad OTH exome AF: 0.0168

GnomAD4 exome AF: 0.0125 AC: 18299 AN: 1458798 Hom.: 3007 Cov.: 31 AF XY: 0.0108 AC XY: 7859 AN XY: 725668

Gnomad4 AFR exome AF: 0.410

Gnomad4 AMR exome AF: 0.0249

Gnomad4 ASJ exome AF: 0.00771

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000801

Gnomad4 FIN exome AF: 0.000135

Gnomad4 NFE exome AF: 0.00137

Gnomad4 OTH exome AF: 0.0264

GnomAD4 genome AF: 0.119 AC: 18062 AN: 152254 Hom.: 3526 Cov.: 32 AF XY: 0.113 AC XY: 8434 AN XY: 74450

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.0514

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00246

Gnomad4 OTH AF: 0.0861

Alfa AF: 0.0112 Hom.: 105

Bravo AF: 0.133

Asia WGS AF: 0.0180 AC: 64 AN: 3478

EpiCase AF: 0.00213

EpiControl AF: 0.00238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	10
DANN	Benign	0.94
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		3.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs35363135; hg19: chr11-67196049;