rs16898963

Variant names:

• chr6-166469176-A-C
• rs16898963
• NM_021135.6:c.972+665T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021135.6(RPS6KA2):​c.972+665T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,144 control chromosomes in the GnomAD database, including 1,365 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 0.13 (1365 hom., cov: 33)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.133 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	NM_021135.6	MANE Select	c.972+665T>G		intron	N/A	NP_066958.2
	RPS6KA2	NM_001318936.2		c.1047+665T>G		intron	N/A	NP_001305865.2	F2Z2J1
	RPS6KA2	NM_001006932.3		c.996+665T>G		intron	N/A	NP_001006933.3	Q15349-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	ENST00000265678.9	TSL:1 MANE Select	c.972+665T>G		intron	N/A	ENSP00000265678.4	Q15349-1
	RPS6KA2	ENST00000481261.6	TSL:1	c.705+665T>G		intron	N/A	ENSP00000422484.1	B7Z3B5
	RPS6KA2	ENST00000510118.5	TSL:2	c.1047+665T>G		intron	N/A	ENSP00000422435.1	F2Z2J1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20490 AN: 152026 Hom.: 1366 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.135 AC: 20494 AN: 152144 Hom.: 1365 Cov.: 33 AF XY: 0.133 AC XY: 9895 AN XY: 74398

African (AFR) AF: 0.136 AC: 5628 AN: 41494

American (AMR) AF: 0.136 AC: 2073 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 536 AN: 3470

East Asian (EAS) AF: 0.124 AC: 641 AN: 5178

South Asian (SAS) AF: 0.136 AC: 654 AN: 4818

European-Finnish (FIN) AF: 0.124 AC: 1317 AN: 10604

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.133 AC: 9043 AN: 67988

Other (OTH) AF: 0.143 AC: 301 AN: 2104

Alfa AF: 0.136 Hom.: 2785

Bravo AF: 0.136

Asia WGS AF: 0.129 AC: 447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.62
PhyloP100		0.11
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: rs16898963; hg19: chr6-166882664; COSMIC: COSV55828370; COSMIC: COSV55828370;