rs9459715

Variant names:

• chr6-166687837-T-G
• rs9459715
• NM_001318936.2:c.174+83026A>C

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+83026A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,242 control chromosomes in the GnomAD database, including 1,106 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 0.11 (1106 hom., cov: 32)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_001318936.2	c.174+83026A>C		intron_variant	Intron 3 of 22		NP_001305865.2
RPS6KA2	NM_001006932.3	c.124-149053A>C		intron_variant	Intron 2 of 21		NP_001006933.3
RPS6KA2	NM_001318937.2	c.37+174271A>C		intron_variant	Intron 1 of 18		NP_001305866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000510118.5	c.174+83026A>C		intron_variant	Intron 3 of 22	2		ENSP00000422435.1
RPS6KA2	ENST00000503859.5	c.124-149053A>C		intron_variant	Intron 2 of 21	2		ENSP00000427015.1
RPS6KA2	ENST00000714395.1	c.51+4956A>C		intron_variant	Intron 1 of 20			ENSP00000519662.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16355 AN: 152124 Hom.: 1105 Cov.: 32

Gnomad AFR AF: 0.0827

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.0812

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0864

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.108 AC: 16375 AN: 152242 Hom.: 1106 Cov.: 32 AF XY: 0.108 AC XY: 8016 AN XY: 74444

African (AFR) AF: 0.0831 AC: 3450 AN: 41540

American (AMR) AF: 0.0812 AC: 1242 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3470

East Asian (EAS) AF: 0.327 AC: 1687 AN: 5166

South Asian (SAS) AF: 0.161 AC: 780 AN: 4832

European-Finnish (FIN) AF: 0.0864 AC: 916 AN: 10606

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7558 AN: 68010

Other (OTH) AF: 0.118 AC: 249 AN: 2114

Alfa AF: 0.108 Hom.: 2857

Bravo AF: 0.104

Asia WGS AF: 0.233 AC: 808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.083
DANN	Benign	0.77
PhyloP100		-1.6
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs9459715; hg19: chr6-167101325;