Genetic Variant RPS6KA2:c.100-3466T>C (chr6-166542250-A-G) – 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.100-3466T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.858 in 152,282 control chromosomes in the GnomAD database, including 56,230 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 0.86 ( 56228 hom., cov: 34)

Exomes 𝑓: 0.67 ( 2 hom. )

Consequence

RPS6KA2
NM_021135.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.241

Publications

4 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:

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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=-0.99).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_021135.6 link	c.100-3466T>C		intron_variant	Intron 1 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.100-3466T>C		intron_variant	Intron 1 of 20	1	NM_021135.6	ENSP00000265678.4		Q15349-1

Frequencies

GnomAD3 genomes

AF:

0.858

AC:

130606

AN:

152158

Hom.:

56170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.889

Gnomad AMI

AF:

0.814

Gnomad AMR

AF:

0.905

Gnomad ASJ

AF:

0.817

Gnomad EAS

AF:

0.990

Gnomad SAS

AF:

0.890

Gnomad FIN

AF:

0.819

Gnomad MID

AF:

0.801

Gnomad NFE

AF:

0.826

Gnomad OTH

AF:

0.864

GnomAD4 exome

AF:

0.667

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.858

AC:

130723

AN:

152276

Hom.:

56228

Cov.:

AF XY:

0.860

AC XY:

63988

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.889

AC:

36947

AN:

41556

American (AMR)

AF:

0.905

AC:

13857

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.817

AC:

2836

AN:

3470

East Asian (EAS)

AF:

0.990

AC:

5138

AN:

5190

South Asian (SAS)

AF:

0.890

AC:

4292

AN:

4822

European-Finnish (FIN)

AF:

0.819

AC:

8677

AN:

10596

Middle Eastern (MID)

AF:

0.803

AC:

236

AN:

294

European-Non Finnish (NFE)

AF:

0.826

AC:

56172

AN:

68014

Other (OTH)

AF:

0.865

AC:

1826

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

988

1976

2965

3953

4941

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

892

1784

2676

3568

4460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.839

Hom.:

108294

Bravo

AF:

0.868

Asia WGS

AF:

0.936

AC:

3256

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

4.0

(source)

DANN

Benign

0.39

PhyloP100

0.24

PromoterAI

-0.00060

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over