rs6911624

Variant names:

• chr6-166700561-G-A
• rs6911624
• NM_001318936.2:c.174+70302C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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]

IGF2BP3P1 (HGNC:58596):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318936.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	NM_001318936.2		c.174+70302C>T		intron	N/A	NP_001305865.2	F2Z2J1
	RPS6KA2	NM_001006932.3		c.123+157639C>T		intron	N/A	NP_001006933.3	Q15349-3
	RPS6KA2	NM_001318937.2		c.37+161547C>T		intron	N/A	NP_001305866.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	ENST00000510118.5	TSL:2	c.174+70302C>T		intron	N/A	ENSP00000422435.1	F2Z2J1
	RPS6KA2	ENST00000503859.5	TSL:2	c.123+157639C>T		intron	N/A	ENSP00000427015.1	Q15349-3
	RPS6KA2	ENST00000506565.1	TSL:4	c.174+70302C>T		intron	N/A	ENSP00000425148.1	D6RE03

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

African (AFR) AF: 0.411 AC: 17035 AN: 41422

American (AMR) AF: 0.230 AC: 3506 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 811 AN: 3470

East Asian (EAS) AF: 0.143 AC: 737 AN: 5170

South Asian (SAS) AF: 0.128 AC: 617 AN: 4810

European-Finnish (FIN) AF: 0.201 AC: 2111 AN: 10526

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 11998 AN: 67948

Other (OTH) AF: 0.227 AC: 478 AN: 2106

Alfa AF: 0.201 Hom.: 5973

Bravo AF: 0.258

Asia WGS AF: 0.140 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.4
DANN	Benign	0.59
PhyloP100		2.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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