rs9459678

Variant names:

• chr6-166470493-T-C
• rs9459678
• NM_021135.6:c.908-588A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021135.6(RPS6KA2):​c.908-588A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 152,180 control chromosomes in the GnomAD database, including 15,602 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 0.43 (15602 hom., cov: 33)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 8 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_021135.6	c.908-588A>G		intron_variant	Intron 10 of 20	ENST00000265678.9	NP_066958.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000265678.9	c.908-588A>G		intron_variant	Intron 10 of 20	1	NM_021135.6	ENSP00000265678.4

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65725 AN: 152062 Hom.: 15559 Cov.: 33

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.425

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.432 AC: 65810 AN: 152180 Hom.: 15602 Cov.: 33 AF XY: 0.430 AC XY: 31983 AN XY: 74408

African (AFR) AF: 0.640 AC: 26556 AN: 41504

American (AMR) AF: 0.458 AC: 7002 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1227 AN: 3468

East Asian (EAS) AF: 0.181 AC: 936 AN: 5174

South Asian (SAS) AF: 0.274 AC: 1324 AN: 4824

European-Finnish (FIN) AF: 0.368 AC: 3906 AN: 10608

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23425 AN: 67992

Other (OTH) AF: 0.420 AC: 888 AN: 2112

Alfa AF: 0.364 Hom.: 22449

Bravo AF: 0.447

Asia WGS AF: 0.279 AC: 970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.59
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9459678; hg19: chr6-166883981; COSMIC: COSV55828399;