chr6-166825124-C-A

Variant names:

• chr6-166825124-C-A
• rs1202621
• NM_001318936.2:c.123+33076G>T

Variant summary

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

The NM_001318936.2(RPS6KA2):​c.123+33076G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 152,090 control chromosomes in the GnomAD database, including 26,788 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 0.58 (26788 hom., cov: 33)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.822
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318936.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	NM_001318936.2		c.123+33076G>T		intron	N/A	NP_001305865.2
	RPS6KA2	NM_001006932.3		c.123+33076G>T		intron	N/A	NP_001006933.3
	RPS6KA2	NM_001318937.2		c.37+36984G>T		intron	N/A	NP_001305866.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	ENST00000510118.5	TSL:2	c.123+33076G>T		intron	N/A	ENSP00000422435.1
	RPS6KA2	ENST00000503859.5	TSL:2	c.123+33076G>T		intron	N/A	ENSP00000427015.1
	RPS6KA2	ENST00000506565.1	TSL:4	c.123+33076G>T		intron	N/A	ENSP00000425148.1

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88936 AN: 151972 Hom.: 26791 Cov.: 33

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.585 AC: 88956 AN: 152090 Hom.: 26788 Cov.: 33 AF XY: 0.580 AC XY: 43098 AN XY: 74348

African (AFR) AF: 0.491 AC: 20358 AN: 41484

American (AMR) AF: 0.552 AC: 8431 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 2251 AN: 3466

East Asian (EAS) AF: 0.292 AC: 1511 AN: 5166

South Asian (SAS) AF: 0.580 AC: 2799 AN: 4822

European-Finnish (FIN) AF: 0.578 AC: 6115 AN: 10584

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45286 AN: 67976

Other (OTH) AF: 0.620 AC: 1305 AN: 2106

Alfa AF: 0.639 Hom.: 50737

Bravo AF: 0.578

Asia WGS AF: 0.435 AC: 1513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.21
DANN	Benign	0.66
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1202621; hg19: chr6-167238612;