6-166521707-T-C

Variant names:

• chr6-166521707-T-C
• rs2187911
• NM_021135.6:c.298+9525A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021135.6(RPS6KA2):​c.298+9525A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,970 control chromosomes in the GnomAD database, including 29,470 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 0.62 (29470 hom., cov: 31)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021135.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	NM_021135.6	MANE Select	c.298+9525A>G		intron	N/A	NP_066958.2
	RPS6KA2	NM_001318936.2		c.373+9525A>G		intron	N/A	NP_001305865.2
	RPS6KA2	NM_001006932.3		c.322+9525A>G		intron	N/A	NP_001006933.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	ENST00000265678.9	TSL:1 MANE Select	c.298+9525A>G		intron	N/A	ENSP00000265678.4
	RPS6KA2	ENST00000481261.6	TSL:1	c.31+9525A>G		intron	N/A	ENSP00000422484.1
	RPS6KA2	ENST00000510118.5	TSL:2	c.373+9525A>G		intron	N/A	ENSP00000422435.1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93614 AN: 151852 Hom.: 29469 Cov.: 31

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.616 AC: 93660 AN: 151970 Hom.: 29470 Cov.: 31 AF XY: 0.614 AC XY: 45575 AN XY: 74280

African (AFR) AF: 0.740 AC: 30666 AN: 41436

American (AMR) AF: 0.632 AC: 9646 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2019 AN: 3470

East Asian (EAS) AF: 0.587 AC: 3029 AN: 5156

South Asian (SAS) AF: 0.620 AC: 2979 AN: 4806

European-Finnish (FIN) AF: 0.439 AC: 4635 AN: 10568

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38652 AN: 67942

Other (OTH) AF: 0.605 AC: 1280 AN: 2114

Alfa AF: 0.590 Hom.: 81809

Bravo AF: 0.633

Asia WGS AF: 0.653 AC: 2268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.6
DANN	Benign	0.88
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2187911; hg19: chr6-166935195; COSMIC: COSV55828536;