rs10946164

Positions:

• chr6-166418206-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.1938+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,494,118 control chromosomes in the GnomAD database, including 130,826 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 (9140 hom., cov: 32)
  • Exomes 𝑓: 0.42 (121686 hom.)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98

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]

LOC124901460 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA2	NM_021135.6	c.1938+19G>A		intron_variant		ENST00000265678.9	NP_066958.2
LOC124901460	XR_007059866.1	n.765-3435C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000265678.9	c.1938+19G>A		intron_variant		1	NM_021135.6	ENSP00000265678	P1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47073 AN: 151912 Hom.: 9139 Cov.: 32

Gnomad AFR AF: 0.0786

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.351

GnomAD3 exomes AF: 0.358 AC: 85969 AN: 240178 Hom.: 17280 AF XY: 0.374 AC XY: 48619 AN XY: 129946

Gnomad AFR exome AF: 0.0701

Gnomad AMR exome AF: 0.208

Gnomad ASJ exome AF: 0.434

Gnomad EAS exome AF: 0.200

Gnomad SAS exome AF: 0.433

Gnomad FIN exome AF: 0.347

Gnomad NFE exome AF: 0.441

Gnomad OTH exome AF: 0.401

GnomAD4 exome AF: 0.418 AC: 560390 AN: 1342088 Hom.: 121686 Cov.: 19 AF XY: 0.420 AC XY: 283029 AN XY: 673444

Gnomad4 AFR exome AF: 0.0668

Gnomad4 AMR exome AF: 0.218

Gnomad4 ASJ exome AF: 0.426

Gnomad4 EAS exome AF: 0.217

Gnomad4 SAS exome AF: 0.433

Gnomad4 FIN exome AF: 0.356

Gnomad4 NFE exome AF: 0.446

Gnomad4 OTH exome AF: 0.405

GnomAD4 genome AF: 0.310 AC: 47061 AN: 152030 Hom.: 9140 Cov.: 32 AF XY: 0.305 AC XY: 22671 AN XY: 74320

Gnomad4 AFR AF: 0.0783

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.352

Alfa AF: 0.410 Hom.: 16001

Bravo AF: 0.294

Asia WGS AF: 0.303 AC: 1053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.017
DANN	Benign	0.39

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: rs10946164; hg19: chr6-166831694; COSMIC: COSV55819486;