rs3823200

Variant names:

• chr6-166572735-T-A
• rs3823200
• NM_021135.6:c.100-33951A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-166572735-T-A
• chr6-166572735-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.100-33951A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,060 control chromosomes in the GnomAD database, including 2,919 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 0.17 (2919 hom., cov: 33)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.16
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_021135.6	c.100-33951A>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.100-33951A>T		intron_variant	Intron 1 of 20	1	NM_021135.6	ENSP00000265678.4

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25315 AN: 151942 Hom.: 2916 Cov.: 33

Gnomad AFR AF: 0.0491

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.166 AC: 25311 AN: 152060 Hom.: 2919 Cov.: 33 AF XY: 0.173 AC XY: 12856 AN XY: 74366

African (AFR) AF: 0.0490 AC: 2031 AN: 41474

American (AMR) AF: 0.274 AC: 4195 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 815 AN: 3464

East Asian (EAS) AF: 0.496 AC: 2558 AN: 5156

South Asian (SAS) AF: 0.303 AC: 1462 AN: 4824

European-Finnish (FIN) AF: 0.177 AC: 1871 AN: 10576

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11672 AN: 67956

Other (OTH) AF: 0.201 AC: 424 AN: 2112

Alfa AF: 0.153 Hom.: 270

Bravo AF: 0.168

Asia WGS AF: 0.366 AC: 1272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.22
DANN	Benign	0.85
PhyloP100		-3.2
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: rs3823200; hg19: chr6-166986223; COSMIC: COSV55828662;