rs12208871

Variant names:

• chr6-166460335-C-T
• rs12208871
• NM_021135.6:c.973-784G>A

Variant summary

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

The NM_021135.6(RPS6KA2):​c.973-784G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,280 control chromosomes in the GnomAD database, including 1,235 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 0.12 (1235 hom., cov: 33)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_021135.6	c.973-784G>A		intron_variant	Intron 11 of 20	ENST00000265678.9	NP_066958.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000265678.9	c.973-784G>A		intron_variant	Intron 11 of 20	1	NM_021135.6	ENSP00000265678.4

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18528 AN: 152162 Hom.: 1235 Cov.: 33

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.0916

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.0979

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.122 AC: 18535 AN: 152280 Hom.: 1235 Cov.: 33 AF XY: 0.118 AC XY: 8817 AN XY: 74448

African (AFR) AF: 0.0927 AC: 3854 AN: 41554

American (AMR) AF: 0.169 AC: 2592 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0916 AC: 318 AN: 3470

East Asian (EAS) AF: 0.0231 AC: 120 AN: 5184

South Asian (SAS) AF: 0.0984 AC: 475 AN: 4828

European-Finnish (FIN) AF: 0.117 AC: 1246 AN: 10608

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9506 AN: 68022

Other (OTH) AF: 0.140 AC: 296 AN: 2112

Alfa AF: 0.136 Hom.: 3027

Bravo AF: 0.126

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.40
DANN	Benign	0.72
PhyloP100		-1.3
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: rs12208871; hg19: chr6-166873823;