6-166551547-T-C

Position:

• chr6-166551547-T-C

Variant summary

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

The NM_021135.6(RPS6KA2):​c.100-12763A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,218 control chromosomes in the GnomAD database, including 2,181 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 0.14 (2181 hom., cov: 33)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA2	NM_021135.6	c.100-12763A>G		intron_variant		ENST00000265678.9	NP_066958.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000265678.9	c.100-12763A>G		intron_variant		1	NM_021135.6	ENSP00000265678.4

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22011 AN: 152100 Hom.: 2181 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.0506

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0996

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.145 AC: 22029 AN: 152218 Hom.: 2181 Cov.: 33 AF XY: 0.151 AC XY: 11243 AN XY: 74412

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.0506

Gnomad4 NFE AF: 0.0996

Gnomad4 OTH AF: 0.149

Alfa AF: 0.120 Hom.: 1595

Bravo AF: 0.159

Asia WGS AF: 0.364 AC: 1269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.31

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: rs3778405; hg19: chr6-166965035;