rs2049957

Variant names:

• chr6-166437832-G-A
• rs2049957
• NM_021135.6:c.1333-5342C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-166437832-G-A
• chr6-166437832-G-C
• chr6-166437832-G-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.1333-5342C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,002 control chromosomes in the GnomAD database, including 20,164 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 0.51 (20164 hom., cov: 32)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.86
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_021135.6	c.1333-5342C>T		intron_variant	Intron 14 of 20	ENST00000265678.9	NP_066958.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000265678.9	c.1333-5342C>T		intron_variant	Intron 14 of 20	1	NM_021135.6	ENSP00000265678.4

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78121 AN: 151884 Hom.: 20158 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.514 AC: 78157 AN: 152002 Hom.: 20164 Cov.: 32 AF XY: 0.513 AC XY: 38149 AN XY: 74324

African (AFR) AF: 0.515 AC: 21340 AN: 41476

American (AMR) AF: 0.479 AC: 7319 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1832 AN: 3452

East Asian (EAS) AF: 0.478 AC: 2460 AN: 5150

South Asian (SAS) AF: 0.370 AC: 1784 AN: 4822

European-Finnish (FIN) AF: 0.606 AC: 6404 AN: 10566

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35398 AN: 67936

Other (OTH) AF: 0.491 AC: 1036 AN: 2108

Alfa AF: 0.507 Hom.: 33738

Bravo AF: 0.504

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.45
DANN	Benign	0.56
PhyloP100		-2.9
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: rs2049957; hg19: chr6-166851320;