rs6926393

Positions:

• chr6-166470723-A-G

Variant summary

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

The NM_021135.6(RPS6KA2):​c.908-818T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,104 control chromosomes in the GnomAD database, including 9,673 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 0.35 (9673 hom., cov: 33)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA2	NM_021135.6	c.908-818T>C		intron_variant		ENST00000265678.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA2	ENST00000265678.9	c.908-818T>C		intron_variant		1	NM_021135.6	P1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53407 AN: 151986 Hom.: 9659 Cov.: 33

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.351 AC: 53461 AN: 152104 Hom.: 9673 Cov.: 33 AF XY: 0.355 AC XY: 26357 AN XY: 74348

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.363

Alfa AF: 0.310 Hom.: 7712

Bravo AF: 0.355

Asia WGS AF: 0.436 AC: 1517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.35
DANN	Benign	0.42

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: rs6926393; hg19: chr6-166884211; COSMIC: COSV55826586;