11-67433150-T-G

Position:

• chr11-67433150-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003952.3(RPS6KB2):​c.732T>G​(p.Ser244Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPS6KB2 NM_003952.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.38

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]

RPS6KB2-AS1 (HGNC:53744): (RPS6KB2 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19812164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KB2	NM_003952.3	c.732T>G	p.Ser244Arg	missense_variant	9/15	ENST00000312629.10	NP_003943.2
RPS6KB2	XM_047427395.1	c.732T>G	p.Ser244Arg	missense_variant	9/11		XP_047283351.1
RPS6KB2	XM_006718656.4	c.132T>G	p.Ser44Arg	missense_variant	5/11		XP_006718719.1
RPS6KB2	XM_047427396.1	c.707+108T>G		intron_variant			XP_047283352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KB2	ENST00000312629.10	c.732T>G	p.Ser244Arg	missense_variant	9/15	1	NM_003952.3	ENSP00000308413.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2024

The c.732T>G (p.S244R) alteration is located in exon 9 (coding exon 9) of the RPS6KB2 gene. This alteration results from a T to G substitution at nucleotide position 732, causing the serine (S) at amino acid position 244 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.30	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.68	N
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.22
Sift	Benign	0.49	T
Sift4G	Benign	0.56	T
Polyphen		0.0090	B
Vest4		0.48
MutPred		0.50		Gain of MoRF binding (P = 0.0184);
MVP		0.34
MPC		0.14
ClinPred		0.16	T
GERP RS		-1.5
Varity_R		0.36
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr11-67200621;