6-166748083-A-G

Variant summary

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

The NM_001318936.2(RPS6KA2):​c.174+22780T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,066 control chromosomes in the GnomAD database, including 34,497 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 0.66 ( 34497 hom., cov: 32)

Consequence

RPS6KA2
NM_001318936.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.699
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=-0.93).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPS6KA2NM_001006932.3 linkuse as main transcriptc.123+110117T>C intron_variant
RPS6KA2NM_001318936.2 linkuse as main transcriptc.174+22780T>C intron_variant
RPS6KA2NM_001318937.2 linkuse as main transcriptc.37+114025T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPS6KA2ENST00000503859.5 linkuse as main transcriptc.123+110117T>C intron_variant 2 Q15349-3
RPS6KA2ENST00000506565.1 linkuse as main transcriptc.174+22780T>C intron_variant 4
RPS6KA2ENST00000507371.5 linkuse as main transcriptc.51+9444T>C intron_variant 3

Frequencies

GnomAD3 genomes
AF:
0.662
AC:
100636
AN:
151950
Hom.:
34445
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.849
Gnomad AMI
AF:
0.499
Gnomad AMR
AF:
0.580
Gnomad ASJ
AF:
0.567
Gnomad EAS
AF:
0.645
Gnomad SAS
AF:
0.665
Gnomad FIN
AF:
0.601
Gnomad MID
AF:
0.570
Gnomad NFE
AF:
0.586
Gnomad OTH
AF:
0.637
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.663
AC:
100749
AN:
152066
Hom.:
34497
Cov.:
32
AF XY:
0.662
AC XY:
49221
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.849
Gnomad4 AMR
AF:
0.580
Gnomad4 ASJ
AF:
0.567
Gnomad4 EAS
AF:
0.645
Gnomad4 SAS
AF:
0.665
Gnomad4 FIN
AF:
0.601
Gnomad4 NFE
AF:
0.586
Gnomad4 OTH
AF:
0.639
Alfa
AF:
0.596
Hom.:
42348
Bravo
AF:
0.666
Asia WGS
AF:
0.689
AC:
2396
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
4.0
DANN
Benign
0.53

Splicing

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: rs1883361; hg19: chr6-167161571; COSMIC: COSV72315598; API