rs1040446

Variant names:

• chr6-166671520-A-C
• rs1040446
• NM_001318936.2:c.174+99343T>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+99343T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 151,960 control chromosomes in the GnomAD database, including 4,743 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 0.21 (4743 hom., cov: 32)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 2 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]

ENSG00000301701 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.416 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.174+99343T>G		intron	N/A	NP_001305865.2	F2Z2J1
	RPS6KA2	NM_001006932.3		c.124-132736T>G		intron	N/A	NP_001006933.3	Q15349-3
	RPS6KA2	NM_001318937.2		c.38-161196T>G		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.174+99343T>G		intron	N/A	ENSP00000422435.1	F2Z2J1
	RPS6KA2	ENST00000503859.5	TSL:2	c.124-132736T>G		intron	N/A	ENSP00000427015.1	Q15349-3
	RPS6KA2	ENST00000714395.1		c.51+21273T>G		intron	N/A	ENSP00000519662.1	A0AAQ5BI00

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31822 AN: 151842 Hom.: 4723 Cov.: 32

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.210 AC: 31891 AN: 151960 Hom.: 4743 Cov.: 32 AF XY: 0.211 AC XY: 15653 AN XY: 74268

African (AFR) AF: 0.421 AC: 17422 AN: 41374

American (AMR) AF: 0.183 AC: 2798 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 530 AN: 3472

East Asian (EAS) AF: 0.187 AC: 965 AN: 5170

South Asian (SAS) AF: 0.174 AC: 838 AN: 4808

European-Finnish (FIN) AF: 0.146 AC: 1544 AN: 10574

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7160 AN: 67968

Other (OTH) AF: 0.196 AC: 414 AN: 2110

Alfa AF: 0.175 Hom.: 1342

Bravo AF: 0.221

Asia WGS AF: 0.218 AC: 759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.076
DANN	Benign	0.34
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: rs1040446; hg19: chr6-167085008;