rs9295348

chr6-166465220-A-Cchr6-166465220-A-T

Variant summary

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

The NM_021135.6(RPS6KA2):c.972+4621T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,106 control chromosomes in the GnomAD database, including 8,430 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 0.33 (8429 hom., cov: 33)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA2	NM_021135.6	c.972+4621T>G		intron_variant		ENST00000265678.9
RPS6KA2-IT1	NR_046793.1	n.59+105T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA2	ENST00000265678.9	c.972+4621T>G		intron_variant		1	NM_021135.6	P1
RPS6KA2-IT1	ENST00000416770.1	n.59+105T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49874 AN: 151980 Hom.: 8403 Cov.: 33

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.329

GnomAD4 exome AF: 0.500 AC: 4 AN: 8 Hom.: 1 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.328 AC: 49939 AN: 152098 Hom.: 8429 Cov.: 33 AF XY: 0.335 AC XY: 24894 AN XY: 74346

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.332

Alfa AF: 0.287 Hom.: 8662

Bravo AF: 0.333

Asia WGS AF: 0.420 AC: 1462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.4
Dann	Benign	0.68

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: rs9295348; hg19: chr6-166878708;