rs12199759

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021135.6(RPS6KA2):​c.908-1372T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,166 control chromosomes in the GnomAD database, including 2,587 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 0.18 ( 2587 hom., cov: 33)

Consequence

RPS6KA2
NM_021135.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.72
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPS6KA2NM_021135.6 linkuse as main transcriptc.908-1372T>C intron_variant ENST00000265678.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPS6KA2ENST00000265678.9 linkuse as main transcriptc.908-1372T>C intron_variant 1 NM_021135.6 P1Q15349-1

Frequencies

GnomAD3 genomes
AF:
0.182
AC:
27696
AN:
152048
Hom.:
2586
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.171
Gnomad AMI
AF:
0.235
Gnomad AMR
AF:
0.188
Gnomad ASJ
AF:
0.146
Gnomad EAS
AF:
0.0465
Gnomad SAS
AF:
0.171
Gnomad FIN
AF:
0.221
Gnomad MID
AF:
0.180
Gnomad NFE
AF:
0.194
Gnomad OTH
AF:
0.176
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.182
AC:
27701
AN:
152166
Hom.:
2587
Cov.:
33
AF XY:
0.181
AC XY:
13472
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.171
Gnomad4 AMR
AF:
0.188
Gnomad4 ASJ
AF:
0.146
Gnomad4 EAS
AF:
0.0466
Gnomad4 SAS
AF:
0.172
Gnomad4 FIN
AF:
0.221
Gnomad4 NFE
AF:
0.194
Gnomad4 OTH
AF:
0.175
Alfa
AF:
0.187
Hom.:
3902
Bravo
AF:
0.178
Asia WGS
AF:
0.125
AC:
438
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.69
DANN
Benign
0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs12199759; hg19: chr6-166884765; API