rs4709127

Positions:

• chr6-166706807-T-C

Variant summary

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

The NM_001318936.2(RPS6KA2):​c.174+64056A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 152,150 control chromosomes in the GnomAD database, including 39,886 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 0.72 (39886 hom., cov: 33)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA2	NM_001006932.3	c.123+151393A>G		intron_variant
RPS6KA2	NM_001318936.2	c.174+64056A>G		intron_variant
RPS6KA2	NM_001318937.2	c.37+155301A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA2	ENST00000503859.5	c.123+151393A>G		intron_variant		2
RPS6KA2	ENST00000506565.1	c.174+64056A>G		intron_variant		4
RPS6KA2	ENST00000507371.5	c.51+50720A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109948 AN: 152032 Hom.: 39861 Cov.: 33

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.723 AC: 110020 AN: 152150 Hom.: 39886 Cov.: 33 AF XY: 0.726 AC XY: 54033 AN XY: 74384

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.708

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.844

Gnomad4 SAS AF: 0.851

Gnomad4 FIN AF: 0.741

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.714

Alfa AF: 0.721 Hom.: 10939

Bravo AF: 0.719

Asia WGS AF: 0.853 AC: 2966 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	0.44
DANN	Benign	0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4709127; hg19: chr6-167120295; COSMIC: COSV71990123; COSMIC: COSV71990123;