6-166560734-T-C

Variant summary

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

The NM_021135.6(RPS6KA2):c.100-21950A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,902 control chromosomes in the GnomAD database, including 20,388 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 0.49 (20388 hom., cov: 31)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA2	NM_021135.6	c.100-21950A>G		intron_variant		ENST00000265678.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA2	ENST00000265678.9	c.100-21950A>G		intron_variant		1	NM_021135.6	P1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74260 AN: 151784 Hom.: 20350 Cov.: 31

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.489 AC: 74354 AN: 151902 Hom.: 20388 Cov.: 31 AF XY: 0.490 AC XY: 36409 AN XY: 74252

Gnomad4 AFR AF: 0.718

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.696

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.470

Alfa AF: 0.386 Hom.: 14837

Bravo AF: 0.516

Asia WGS AF: 0.667 AC: 2318 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	0.019
Dann	Benign	0.24

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: rs3799620; hg19: chr6-166974222;