rs411236

chr6-166508605-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.380-323T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 152,018 control chromosomes in the GnomAD database, including 38,973 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 0.71 (38973 hom., cov: 32)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA2	NM_021135.6	c.380-323T>C		intron_variant		ENST00000265678.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA2	ENST00000265678.9	c.380-323T>C		intron_variant		1	NM_021135.6	P1

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108605 AN: 151898 Hom.: 38944 Cov.: 32

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.713

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

GnomAD4 genome AF: 0.715 AC: 108683 AN: 152018 Hom.: 38973 Cov.: 32 AF XY: 0.717 AC XY: 53239 AN XY: 74302

Gnomad4 AFR AF: 0.680

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.675

Gnomad4 EAS AF: 0.678

Gnomad4 SAS AF: 0.734

Gnomad4 FIN AF: 0.798

Gnomad4 NFE AF: 0.719

Gnomad4 OTH AF: 0.714

Alfa AF: 0.713 Hom.: 43811

Bravo AF: 0.708

Asia WGS AF: 0.668 AC: 2327 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	0.075
Dann	Benign	0.23

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: rs411236; hg19: chr6-166922093; COSMIC: COSV55828511; COSMIC: COSV55828511;