rs2049957

chr6-166437832-G-Achr6-166437832-G-Cchr6-166437832-G-T

Variant summary

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

The NM_021135.6(RPS6KA2):c.1333-5342C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,002 control chromosomes in the GnomAD database, including 20,164 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 0.51 (20164 hom., cov: 32)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.86

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA2	NM_021135.6	c.1333-5342C>T		intron_variant		ENST00000265678.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA2	ENST00000265678.9	c.1333-5342C>T		intron_variant		1	NM_021135.6	P1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78121 AN: 151884 Hom.: 20158 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.514 AC: 78157 AN: 152002 Hom.: 20164 Cov.: 32 AF XY: 0.513 AC XY: 38149 AN XY: 74324

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.491

Alfa AF: 0.504 Hom.: 20891

Bravo AF: 0.504

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.45
Dann	Benign	0.56

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: rs2049957; hg19: chr6-166851320;