6-166504356-G-A

Variant names:

• chr6-166504356-G-A
• rs2071941
• NM_021135.6:c.566+150C>T

Variant summary

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

The NM_021135.6(RPS6KA2):​c.566+150C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 541,090 control chromosomes in the GnomAD database, including 12,217 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 0.24 (6402 hom., cov: 33)
  • Exomes 𝑓: 0.15 (5815 hom.)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	NM_021135.6	MANE Select	c.566+150C>T		intron	N/A	NP_066958.2
	RPS6KA2	NM_001318936.2		c.641+150C>T		intron	N/A	NP_001305865.2	F2Z2J1
	RPS6KA2	NM_001006932.3		c.590+150C>T		intron	N/A	NP_001006933.3	Q15349-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	ENST00000265678.9	TSL:1 MANE Select	c.566+150C>T		intron	N/A	ENSP00000265678.4	Q15349-1
	RPS6KA2	ENST00000481261.6	TSL:1	c.299+150C>T		intron	N/A	ENSP00000422484.1	B7Z3B5
	RPS6KA2	ENST00000510118.5	TSL:2	c.641+150C>T		intron	N/A	ENSP00000422435.1	F2Z2J1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36447 AN: 152022 Hom.: 6392 Cov.: 33

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.204

GnomAD4 exome AF: 0.154 AC: 59756 AN: 388950 Hom.: 5815 AF XY: 0.153 AC XY: 31283 AN XY: 204988

African (AFR) AF: 0.485 AC: 4457 AN: 9198

American (AMR) AF: 0.167 AC: 2123 AN: 12742

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 1369 AN: 12072

East Asian (EAS) AF: 0.309 AC: 7933 AN: 25634

South Asian (SAS) AF: 0.160 AC: 5443 AN: 34020

European-Finnish (FIN) AF: 0.131 AC: 4063 AN: 31086

Middle Eastern (MID) AF: 0.200 AC: 399 AN: 1992

European-Non Finnish (NFE) AF: 0.126 AC: 30059 AN: 239458

Other (OTH) AF: 0.172 AC: 3910 AN: 22748

GnomAD4 genome AF: 0.240 AC: 36498 AN: 152140 Hom.: 6402 Cov.: 33 AF XY: 0.238 AC XY: 17709 AN XY: 74400

African (AFR) AF: 0.495 AC: 20538 AN: 41480

American (AMR) AF: 0.173 AC: 2647 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 395 AN: 3470

East Asian (EAS) AF: 0.269 AC: 1389 AN: 5166

South Asian (SAS) AF: 0.167 AC: 805 AN: 4818

European-Finnish (FIN) AF: 0.138 AC: 1466 AN: 10604

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8613 AN: 67986

Other (OTH) AF: 0.209 AC: 442 AN: 2114

Alfa AF: 0.156 Hom.: 4775

Bravo AF: 0.254

Asia WGS AF: 0.234 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.99
DANN	Benign	0.58
PhyloP100		0.029
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: rs2071941; hg19: chr6-166917844; COSMIC: COSV55828467; COSMIC: COSV55828467;