Genetic Variant RPS6KB2:c.78+143T>G (chr11-67428766-T-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_003952.3(RPS6KB2):c.78+143T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000128 in 779,374 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)

Exomes 𝑓: 0.0000013 ( 0 hom. )

Consequence

RPS6KB2
NM_003952.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.275

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
RPS6KB2	NM_003952.3 link	c.78+143T>G	intron_variant	Intron 1 of 14	ENST00000312629.10	NP_003943.2
RPS6KB2	XM_047427395.1 link	c.78+143T>G	intron_variant	Intron 1 of 10		XP_047283351.1
RPS6KB2	XM_047427396.1 link	c.78+143T>G	intron_variant	Intron 1 of 9		XP_047283352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KB2	ENST00000312629.10 link	c.78+143T>G		intron_variant	Intron 1 of 14	1	NM_003952.3	ENSP00000308413.5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000128

AC:

AN:

779374

Hom.:

Cov.:

AF XY:

0.00000249

AC XY:

AN XY:

401468

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19540

American (AMR)

AF:

0.00

AC:

AN:

32478

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18540

East Asian (EAS)

AF:

0.00

AC:

AN:

33022

South Asian (SAS)

AF:

0.0000165

AC:

AN:

60436

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42654

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4390

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

530898

Other (OTH)

AF:

0.00

AC:

AN:

37416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.8

(source)

DANN

Benign

0.69

PhyloP100

-0.28

PromoterAI

0.050

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.95

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.95

Position offset: -1

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