rs9459678

chr6-166470493-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
RPS6KA2	NM_021135.6	c.908-588A>G		intron_variant		ENST00000265678.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA2	ENST00000265678.9	c.908-588A>G		intron_variant		1	NM_021135.6	P1

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

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.420

Alfa AF: 0.357 Hom.: 14660

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

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

Publications

LitVar

Other links and lift over

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