Genetic Variant NM_021135.6:c.2182C>T (chr6-166412782-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_021135.6(RPS6KA2):c.2182C>T(p.Leu728Phe) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L728I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RPS6KA2
NM_021135.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.87

Publications

0 publications found

Variant links:

Genes affected

RPS6KA2 (HGNC:10431): (ribosomal protein S6 kinase A2) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains two non-identical kinase catalytic domains and phosphorylates various substrates, including members of the mitogen-activated kinase (MAPK) signalling pathway. The activity of this protein has been implicated in controlling cell growth and differentiation. Alternative splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jan 2016]

RPS6KA2 links:

LOC124901460 (HGNC:):

LOC124901460 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2835058).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021135.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPS6KA2	NM_021135.6	MANE Select	c.2182C>T	p.Leu728Phe	missense	Exon 21 of 21	NP_066958.2
RPS6KA2	NM_001318936.2		c.2257C>T	p.Leu753Phe	missense	Exon 23 of 23	NP_001305865.2	F2Z2J1
RPS6KA2	NM_001006932.3		c.2206C>T	p.Leu736Phe	missense	Exon 22 of 22	NP_001006933.3	Q15349-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPS6KA2	ENST00000265678.9	TSL:1 MANE Select	c.2182C>T	p.Leu728Phe	missense	Exon 21 of 21	ENSP00000265678.4	Q15349-1
RPS6KA2	ENST00000481261.6	TSL:1	c.1915C>T	p.Leu639Phe	missense	Exon 21 of 21	ENSP00000422484.1	B7Z3B5
RPS6KA2	ENST00000509742.1	TSL:1	n.718C>T		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1446002

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717674

African (AFR)

AF:

0.00

AC:

AN:

33360

American (AMR)

AF:

0.00

AC:

AN:

42254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25634

East Asian (EAS)

AF:

0.00

AC:

AN:

39122

South Asian (SAS)

AF:

0.00

AC:

AN:

82996

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51024

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106052

Other (OTH)

AF:

0.00

AC:

AN:

59814

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

0.00010

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.074

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.067

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.41

MutationAssessor

Uncertain

2.2

PhyloP100

1.9

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.9

REVEL

Benign

0.20

Sift

Benign

0.054

Sift4G

Benign

0.51

Polyphen

0.91

Vest4

0.32

MutPred

0.19

Gain of phosphorylation at T756 (P = 0.1248)

MVP

0.85

MPC

1.2

ClinPred

0.83

GERP RS

4.7

Varity_R

0.13

gMVP

0.57

Mutation Taster

=57/43

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over