6-166565558-T-C

Variant names:

• chr6-166565558-T-C
• rs3778401
• NM_021135.6:c.100-26774A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021135.6(RPS6KA2):​c.100-26774A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 152,024 control chromosomes in the GnomAD database, including 24,432 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 0.56 (24432 hom., cov: 34)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.29
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021135.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	NM_021135.6	MANE Select	c.100-26774A>G		intron	N/A	NP_066958.2
	RPS6KA2	NM_001318936.2		c.175-26774A>G		intron	N/A	NP_001305865.2
	RPS6KA2	NM_001006932.3		c.124-26774A>G		intron	N/A	NP_001006933.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	ENST00000265678.9	TSL:1 MANE Select	c.100-26774A>G		intron	N/A	ENSP00000265678.4
	RPS6KA2	ENST00000510118.5	TSL:2	c.175-26774A>G		intron	N/A	ENSP00000422435.1
	RPS6KA2	ENST00000967274.1		c.100-26774A>G		intron	N/A	ENSP00000637333.1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84971 AN: 151906 Hom.: 24391 Cov.: 34

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.560 AC: 85066 AN: 152024 Hom.: 24432 Cov.: 34 AF XY: 0.566 AC XY: 42060 AN XY: 74306

African (AFR) AF: 0.603 AC: 25037 AN: 41508

American (AMR) AF: 0.690 AC: 10566 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1992 AN: 3466

East Asian (EAS) AF: 0.838 AC: 4336 AN: 5172

South Asian (SAS) AF: 0.615 AC: 2964 AN: 4818

European-Finnish (FIN) AF: 0.521 AC: 5509 AN: 10566

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 32951 AN: 67870

Other (OTH) AF: 0.555 AC: 1171 AN: 2110

Alfa AF: 0.517 Hom.: 27029

Bravo AF: 0.575

Asia WGS AF: 0.696 AC: 2425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.46
DANN	Benign	0.19
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3778401; hg19: chr6-166979046; COSMIC: COSV55817971;