rs1040446

Positions:

• chr6-166671520-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318936.2(RPS6KA2):​c.174+99343T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 151,960 control chromosomes in the GnomAD database, including 4,743 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 0.21 (4743 hom., cov: 32)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA2	NM_001006932.3	c.124-132736T>G		intron_variant
RPS6KA2	NM_001318936.2	c.174+99343T>G		intron_variant
RPS6KA2	NM_001318937.2	c.38-161196T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA2	ENST00000503859.5	c.124-132736T>G		intron_variant		2
RPS6KA2	ENST00000506565.1	c.174+99343T>G		intron_variant		4
RPS6KA2	ENST00000507371.5	c.51+86007T>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31822 AN: 151842 Hom.: 4723 Cov.: 32

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.210 AC: 31891 AN: 151960 Hom.: 4743 Cov.: 32 AF XY: 0.211 AC XY: 15653 AN XY: 74268

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.196

Alfa AF: 0.180 Hom.: 809

Bravo AF: 0.221

Asia WGS AF: 0.218 AC: 759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.076
DANN	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1040446; hg19: chr6-167085008;