rs9295355

Variant names:

• chr6-166602695-T-A
• rs9295355
• NM_021135.6:c.99+24226A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-166602695-T-A
• chr6-166602695-T-C

Variant summary

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

The NM_021135.6(RPS6KA2):​c.99+24226A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,986 control chromosomes in the GnomAD database, including 9,485 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 0.35 (9485 hom., cov: 33)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_021135.6	c.99+24226A>T		intron_variant	Intron 1 of 20	ENST00000265678.9	NP_066958.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000265678.9	c.99+24226A>T		intron_variant	Intron 1 of 20	1	NM_021135.6	ENSP00000265678.4

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52476 AN: 151866 Hom.: 9453 Cov.: 33

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.346 AC: 52571 AN: 151986 Hom.: 9485 Cov.: 33 AF XY: 0.346 AC XY: 25667 AN XY: 74274

African (AFR) AF: 0.429 AC: 17788 AN: 41446

American (AMR) AF: 0.362 AC: 5525 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1270 AN: 3470

East Asian (EAS) AF: 0.509 AC: 2638 AN: 5178

South Asian (SAS) AF: 0.418 AC: 2011 AN: 4814

European-Finnish (FIN) AF: 0.241 AC: 2552 AN: 10568

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19575 AN: 67928

Other (OTH) AF: 0.358 AC: 757 AN: 2112

Alfa AF: 0.152 Hom.: 270

Bravo AF: 0.361

Asia WGS AF: 0.462 AC: 1604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.21
DANN	Benign	0.45
PhyloP100		-0.33
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: rs9295355; hg19: chr6-167016183;