rs6935542

Variant names:

• chr6-166484244-A-G
• rs6935542
• NM_021135.6:c.907+4589T>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.907+4589T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,262 control chromosomes in the GnomAD database, including 2,655 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 0.18 (2655 hom., cov: 33)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 6 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=-1.07).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021135.6. 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_021135.6	MANE Select	c.907+4589T>C		intron	N/A	NP_066958.2
	RPS6KA2	NM_001318936.2		c.982+4589T>C		intron	N/A	NP_001305865.2
	RPS6KA2	NM_001006932.3		c.931+4589T>C		intron	N/A	NP_001006933.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	ENST00000265678.9	TSL:1 MANE Select	c.907+4589T>C		intron	N/A	ENSP00000265678.4
	RPS6KA2	ENST00000481261.6	TSL:1	c.640+4589T>C		intron	N/A	ENSP00000422484.1
	RPS6KA2	ENST00000510118.5	TSL:2	c.982+4589T>C		intron	N/A	ENSP00000422435.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26714 AN: 152144 Hom.: 2647 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0943

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.176 AC: 26760 AN: 152262 Hom.: 2655 Cov.: 33 AF XY: 0.176 AC XY: 13109 AN XY: 74450

African (AFR) AF: 0.266 AC: 11029 AN: 41528

American (AMR) AF: 0.206 AC: 3146 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3468

East Asian (EAS) AF: 0.0937 AC: 486 AN: 5186

South Asian (SAS) AF: 0.171 AC: 823 AN: 4822

European-Finnish (FIN) AF: 0.144 AC: 1533 AN: 10618

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8942 AN: 68018

Other (OTH) AF: 0.163 AC: 344 AN: 2112

Alfa AF: 0.151 Hom.: 1101

Bravo AF: 0.184

Asia WGS AF: 0.161 AC: 558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.17
DANN	Benign	0.37
PhyloP100		-1.6
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: rs6935542; hg19: chr6-166897732;