Genetic Variant RPS6KA2:c.566+150C>T (chr6-166504356-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021135.6(RPS6KA2):c.566+150C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 541,090 control chromosomes in the GnomAD database, including 12,217 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 0.24 ( 6402 hom., cov: 33)

Exomes 𝑓: 0.15 ( 5815 hom. )

Consequence

RPS6KA2
NM_021135.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0290

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_021135.6 link	c.566+150C>T		intron_variant	Intron 6 of 20	ENST00000265678.9	NP_066958.2	Q15349-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000265678.9 link	c.566+150C>T		intron_variant	Intron 6 of 20	1	NM_021135.6	ENSP00000265678.4		Q15349-1

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36447

AN:

152022

Hom.:

6392

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.153

Gnomad AMR

AF:

0.173

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.269

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.204

GnomAD4 exome

AF:

0.154

AC:

59756

AN:

388950

Hom.:

5815

AF XY:

0.153

AC XY:

31283

AN XY:

204988

show subpopulations

African (AFR)

AF:

0.485

AC:

4457

AN:

9198

American (AMR)

AF:

0.167

AC:

2123

AN:

12742

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

1369

AN:

12072

East Asian (EAS)

AF:

0.309

AC:

7933

AN:

25634

South Asian (SAS)

AF:

0.160

AC:

5443

AN:

34020

European-Finnish (FIN)

AF:

0.131

AC:

4063

AN:

31086

Middle Eastern (MID)

AF:

0.200

AC:

399

AN:

1992

European-Non Finnish (NFE)

AF:

0.126

AC:

30059

AN:

239458

Other (OTH)

AF:

0.172

AC:

3910

AN:

22748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

2254

4508

6763

9017

11271

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.240

AC:

36498

AN:

152140

Hom.:

6402

Cov.:

AF XY:

0.238

AC XY:

17709

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.495

AC:

20538

AN:

41480

American (AMR)

AF:

0.173

AC:

2647

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

395

AN:

3470

East Asian (EAS)

AF:

0.269

AC:

1389

AN:

5166

South Asian (SAS)

AF:

0.167

AC:

805

AN:

4818

European-Finnish (FIN)

AF:

0.138

AC:

1466

AN:

10604

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.127

AC:

8613

AN:

67986

Other (OTH)

AF:

0.209

AC:

442

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1255

2509

3764

5018

6273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.156

Hom.:

4775

Bravo

AF:

0.254

Asia WGS

AF:

0.234

AC:

813

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.99

(source)

DANN

Benign

0.58

PhyloP100

0.029

Mutation Taster

=100/0

polymorphism (auto)

(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.

chr6-166504356-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over