rs6906202

Variant names:

• chr6-166686610-T-C
• rs6906202
• NM_001318936.2:c.174+84253A>G

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+84253A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,056 control chromosomes in the GnomAD database, including 11,205 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 (11205 hom., cov: 32)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 1 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	NM_001318936.2		c.174+84253A>G		intron	N/A	NP_001305865.2
	RPS6KA2	NM_001006932.3		c.124-147826A>G		intron	N/A	NP_001006933.3
	RPS6KA2	NM_001318937.2		c.37+175498A>G		intron	N/A	NP_001305866.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	ENST00000510118.5	TSL:2	c.174+84253A>G		intron	N/A	ENSP00000422435.1
	RPS6KA2	ENST00000503859.5	TSL:2	c.124-147826A>G		intron	N/A	ENSP00000427015.1
	RPS6KA2	ENST00000714395.1		c.51+6183A>G		intron	N/A	ENSP00000519662.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53459 AN: 151938 Hom.: 11177 Cov.: 32

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.352 AC: 53534 AN: 152056 Hom.: 11205 Cov.: 32 AF XY: 0.348 AC XY: 25874 AN XY: 74334

African (AFR) AF: 0.592 AC: 24514 AN: 41432

American (AMR) AF: 0.213 AC: 3253 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1013 AN: 3470

East Asian (EAS) AF: 0.356 AC: 1837 AN: 5154

South Asian (SAS) AF: 0.328 AC: 1581 AN: 4820

European-Finnish (FIN) AF: 0.233 AC: 2470 AN: 10594

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17742 AN: 67976

Other (OTH) AF: 0.338 AC: 716 AN: 2116

Alfa AF: 0.313 Hom.: 1058

Bravo AF: 0.359

Asia WGS AF: 0.367 AC: 1273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.44
PhyloP100		-1.4
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: rs6906202; hg19: chr6-167100098; COSMIC: COSV107538693;