6-166700561-G-A

Position:

• chr6-166700561-G-A

Variant summary

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

The NM_001318936.2(RPS6KA2):​c.174+70302C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,924 control chromosomes in the GnomAD database, including 5,485 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 0.25 (5485 hom., cov: 33)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74

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=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA2	NM_001006932.3	c.123+157639C>T		intron_variant			NP_001006933.3
RPS6KA2	NM_001318936.2	c.174+70302C>T		intron_variant			NP_001305865.2
RPS6KA2	NM_001318937.2	c.37+161547C>T		intron_variant			NP_001305866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000503859.5	c.123+157639C>T		intron_variant		2		ENSP00000427015
RPS6KA2	ENST00000506565.1	c.174+70302C>T		intron_variant		4		ENSP00000425148
RPS6KA2	ENST00000507371.5	c.51+56966C>T		intron_variant		3		ENSP00000423114

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37446 AN: 151806 Hom.: 5472 Cov.: 33

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.247 AC: 37494 AN: 151924 Hom.: 5485 Cov.: 33 AF XY: 0.245 AC XY: 18191 AN XY: 74242

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.227

Alfa AF: 0.195 Hom.: 3410

Bravo AF: 0.258

Asia WGS AF: 0.140 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.4
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6911624; hg19: chr6-167114049; COSMIC: COSV71989996; COSMIC: COSV71989996;