rs9347128

Positions:

• chr6-166460812-C-G
• chr6-166460812-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021135.6(RPS6KA2):​c.973-1261G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,178 control chromosomes in the GnomAD database, including 25,561 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 0.55 (25553 hom., cov: 32)
  • Exomes 𝑓: 0.43 (8 hom.)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.907

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]

RPS6KA2-IT1 (HGNC:41378): (RPS6KA2 intronic transcript 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA2	NM_021135.6	c.973-1261G>C		intron_variant		ENST00000265678.9	NP_066958.2
RPS6KA2-IT1	NR_046793.1	n.430G>C		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000265678.9	c.973-1261G>C		intron_variant		1	NM_021135.6	ENSP00000265678	P1
RPS6KA2-IT1	ENST00000416770.1	n.430G>C		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83427 AN: 151964 Hom.: 25488 Cov.: 32

Gnomad AFR AF: 0.830

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.536

GnomAD4 exome AF: 0.427 AC: 41 AN: 96 Hom.: 8 Cov.: 0 AF XY: 0.432 AC XY: 32 AN XY: 74

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.600

Gnomad4 NFE exome AF: 0.419

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.549 AC: 83551 AN: 152082 Hom.: 25553 Cov.: 32 AF XY: 0.552 AC XY: 41036 AN XY: 74330

Gnomad4 AFR AF: 0.830

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.535

Alfa AF: 0.478 Hom.: 2389

Bravo AF: 0.572

Asia WGS AF: 0.545 AC: 1898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.36
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs9347128; hg19: chr6-166874300;