rs9356529

Variant names:

• chr6-166857651-G-A
• rs9356529
• NM_001318936.2:c.123+549C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-166857651-G-A
• chr6-166857651-G-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.123+549C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 152,066 control chromosomes in the GnomAD database, including 29,223 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 0.58 (29223 hom., cov: 32)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 9 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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.735 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.123+549C>T		intron	N/A	NP_001305865.2	F2Z2J1
	RPS6KA2	NM_001006932.3		c.123+549C>T		intron	N/A	NP_001006933.3	Q15349-3
	RPS6KA2	NM_001318937.2		c.37+4457C>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.123+549C>T		intron	N/A	ENSP00000422435.1	F2Z2J1
	RPS6KA2	ENST00000503859.5	TSL:2	c.123+549C>T		intron	N/A	ENSP00000427015.1	Q15349-3
	RPS6KA2	ENST00000506565.1	TSL:4	c.123+549C>T		intron	N/A	ENSP00000425148.1	D6RE03

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87829 AN: 151948 Hom.: 29223 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.611

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

GnomAD4 genome AF: 0.578 AC: 87832 AN: 152066 Hom.: 29223 Cov.: 32 AF XY: 0.578 AC XY: 43002 AN XY: 74336

African (AFR) AF: 0.217 AC: 8994 AN: 41438

American (AMR) AF: 0.681 AC: 10421 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2321 AN: 3472

East Asian (EAS) AF: 0.609 AC: 3155 AN: 5184

South Asian (SAS) AF: 0.677 AC: 3253 AN: 4806

European-Finnish (FIN) AF: 0.684 AC: 7231 AN: 10566

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50330 AN: 67988

Other (OTH) AF: 0.609 AC: 1283 AN: 2108

Alfa AF: 0.690 Hom.: 160900

Bravo AF: 0.559

Asia WGS AF: 0.564 AC: 1964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.32
DANN	Benign	0.53
PhyloP100		-1.2
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: rs9356529; hg19: chr6-167271139;