rs3799612

Positions:

• chr6-166568152-C-G

Variant summary

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

The NM_021135.6(RPS6KA2):​c.100-29368G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,096 control chromosomes in the GnomAD database, including 4,075 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 0.22 (4075 hom., cov: 32)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA2	NM_021135.6	c.100-29368G>C		intron_variant		ENST00000265678.9	NP_066958.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000265678.9	c.100-29368G>C		intron_variant		1	NM_021135.6	ENSP00000265678	P1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33200 AN: 151978 Hom.: 4067 Cov.: 32

Gnomad AFR AF: 0.0987

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.218 AC: 33212 AN: 152096 Hom.: 4075 Cov.: 32 AF XY: 0.220 AC XY: 16374 AN XY: 74352

Gnomad4 AFR AF: 0.0984

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.223

Alfa AF: 0.231 Hom.: 567

Bravo AF: 0.213

Asia WGS AF: 0.223 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.38

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: rs3799612; hg19: chr6-166981640;