rs16898963

Variant summary

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

The NM_021135.6(RPS6KA2):​c.972+665T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,144 control chromosomes in the GnomAD database, including 1,365 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 0.13 ( 1365 hom., cov: 33)

Consequence

RPS6KA2
NM_021135.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.106
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RPS6KA2NM_021135.6 linkuse as main transcriptc.972+665T>G intron_variant ENST00000265678.9 NP_066958.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RPS6KA2ENST00000265678.9 linkuse as main transcriptc.972+665T>G intron_variant 1 NM_021135.6 ENSP00000265678 P1Q15349-1

Frequencies

GnomAD3 genomes
AF:
0.135
AC:
20490
AN:
152026
Hom.:
1366
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.136
Gnomad AMI
AF:
0.269
Gnomad AMR
AF:
0.136
Gnomad ASJ
AF:
0.154
Gnomad EAS
AF:
0.123
Gnomad SAS
AF:
0.136
Gnomad FIN
AF:
0.124
Gnomad MID
AF:
0.194
Gnomad NFE
AF:
0.133
Gnomad OTH
AF:
0.145
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.135
AC:
20494
AN:
152144
Hom.:
1365
Cov.:
33
AF XY:
0.133
AC XY:
9895
AN XY:
74398
show subpopulations
Gnomad4 AFR
AF:
0.136
Gnomad4 AMR
AF:
0.136
Gnomad4 ASJ
AF:
0.154
Gnomad4 EAS
AF:
0.124
Gnomad4 SAS
AF:
0.136
Gnomad4 FIN
AF:
0.124
Gnomad4 NFE
AF:
0.133
Gnomad4 OTH
AF:
0.143
Alfa
AF:
0.136
Hom.:
2032
Bravo
AF:
0.136
Asia WGS
AF:
0.129
AC:
447
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
2.4
DANN
Benign
0.62

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: rs16898963; hg19: chr6-166882664; COSMIC: COSV55828370; COSMIC: COSV55828370; API