Genetic Variant RPS6KB2:c.458-365C>G (chr11-67432235-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003952.3(RPS6KB2):c.458-365C>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RPS6KB2
NM_003952.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.321

Publications

18 publications found

Variant links:

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 links:

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

RPS6KB2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
RPS6KB2	NM_003952.3 link	c.458-365C>G	intron_variant	Intron 5 of 14	ENST00000312629.10	NP_003943.2
RPS6KB2	XM_047427395.1 link	c.458-365C>G	intron_variant	Intron 5 of 10		XP_047283351.1
RPS6KB2	XM_047427396.1 link	c.458-365C>G	intron_variant	Intron 5 of 9		XP_047283352.1
RPS6KB2	XM_006718656.4 link	c.-401C>G	upstream_gene_variant			XP_006718719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KB2	ENST00000312629.10 link	c.458-365C>G		intron_variant	Intron 5 of 14	1	NM_003952.3	ENSP00000308413.5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

354396

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

196812

African (AFR)

AF:

0.00

AC:

AN:

10528

American (AMR)

AF:

0.00

AC:

AN:

27932

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12974

East Asian (EAS)

AF:

0.00

AC:

AN:

13566

South Asian (SAS)

AF:

0.00

AC:

AN:

59340

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16122

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3114

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

192732

Other (OTH)

AF:

0.00

AC:

AN:

18088

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.13

(source)

DANN

Benign

0.16

PhyloP100

-0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over