rs9348131

Positions:

• chr6-166437310-C-T

Variant summary

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

The NM_021135.6(RPS6KA2):​c.1333-4820G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,046 control chromosomes in the GnomAD database, including 10,845 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 0.31 (10845 hom., cov: 32)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA2	NM_021135.6	c.1333-4820G>A		intron_variant		ENST00000265678.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA2	ENST00000265678.9	c.1333-4820G>A		intron_variant		1	NM_021135.6	P1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47424 AN: 151928 Hom.: 10821 Cov.: 32

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.312 AC: 47498 AN: 152046 Hom.: 10845 Cov.: 32 AF XY: 0.312 AC XY: 23198 AN XY: 74326

Gnomad4 AFR AF: 0.647

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.285

Alfa AF: 0.196 Hom.: 2951

Bravo AF: 0.334

Asia WGS AF: 0.329 AC: 1143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.23
DANN	Benign	0.57

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

Other links and lift over

dbSNP: rs9348131; hg19: chr6-166850798; COSMIC: COSV55817527; COSMIC: COSV55817527;