rs3799647

chr6-166533195-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.217-1882T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.09 in 152,322 control chromosomes in the GnomAD database, including 729 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 0.090 (729 hom., cov: 33)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA2	NM_021135.6	c.217-1882T>C		intron_variant		ENST00000265678.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA2	ENST00000265678.9	c.217-1882T>C		intron_variant		1	NM_021135.6	P1

Frequencies

GnomAD3 genomes AF: 0.0900 AC: 13697 AN: 152202 Hom.: 724 Cov.: 33

Gnomad AFR AF: 0.0371

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0998

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.0691

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0993

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

GnomAD4 genome AF: 0.0900 AC: 13710 AN: 152322 Hom.: 729 Cov.: 33 AF XY: 0.0898 AC XY: 6685 AN XY: 74476

Gnomad4 AFR AF: 0.0371

Gnomad4 AMR AF: 0.0996

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.0683

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0974 Hom.: 425

Bravo AF: 0.0896

Asia WGS AF: 0.0870 AC: 303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.8
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3799647; hg19: chr6-166946683;