rs763187

chr6-166542250-A-G

Variant summary

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

The NM_021135.6(RPS6KA2):c.100-3466T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.858 in 152,282 control chromosomes in the GnomAD database, including 56,230 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 0.86 (56228 hom., cov: 34)
  • Exomes 𝑓: 0.67 (2 hom.)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA2	NM_021135.6	c.100-3466T>C		intron_variant		ENST00000265678.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA2	ENST00000265678.9	c.100-3466T>C		intron_variant		1	NM_021135.6	P1

Frequencies

GnomAD3 genomes AF: 0.858 AC: 130606 AN: 152158 Hom.: 56170 Cov.: 34

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.905

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.864

GnomAD4 exome AF: 0.667 AC: 4 AN: 6 Hom.: 2 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.858 AC: 130723 AN: 152276 Hom.: 56228 Cov.: 34 AF XY: 0.860 AC XY: 63988 AN XY: 74446

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.905

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.990

Gnomad4 SAS AF: 0.890

Gnomad4 FIN AF: 0.819

Gnomad4 NFE AF: 0.826

Gnomad4 OTH AF: 0.865

Alfa AF: 0.834 Hom.: 69968

Bravo AF: 0.868

Asia WGS AF: 0.936 AC: 3256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	4.0
Dann	Benign	0.39

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: rs763187; hg19: chr6-166955738;