rs1202621

chr6-166825124-C-Achr6-166825124-C-T

Variant summary

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

The NM_001318936.2(RPS6KA2):c.123+33076G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 152,090 control chromosomes in the GnomAD database, including 26,788 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 0.58 (26788 hom., cov: 33)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.822

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA2	NM_001006932.3	c.123+33076G>T		intron_variant
RPS6KA2	NM_001318936.2	c.123+33076G>T		intron_variant
RPS6KA2	NM_001318937.2	c.37+36984G>T		intron_variant
RPS6KA2	XM_047419235.1	c.-169+33076G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA2	ENST00000503859.5	c.123+33076G>T		intron_variant		2
RPS6KA2	ENST00000506565.1	c.123+33076G>T		intron_variant		4
RPS6KA2	ENST00000510118.5	c.123+33076G>T		intron_variant		2
RPS6KA2	ENST00000512860.5	c.-169+81234G>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88936 AN: 151972 Hom.: 26791 Cov.: 33

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.585 AC: 88956 AN: 152090 Hom.: 26788 Cov.: 33 AF XY: 0.580 AC XY: 43098 AN XY: 74348

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.649

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.620

Alfa AF: 0.645 Hom.: 40168

Bravo AF: 0.578

Asia WGS AF: 0.435 AC: 1513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.21
Dann	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1202621; hg19: chr6-167238612;