6-166543407-G-A

Variant names:

• chr6-166543407-G-A
• rs6918886
• NM_021135.6:c.100-4623C>T

Variant summary

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

The NM_021135.6(RPS6KA2):​c.100-4623C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,006 control chromosomes in the GnomAD database, including 12,333 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 0.40 (12333 hom., cov: 32)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.988
• Publications: 6 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.543 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	NM_021135.6	MANE Select	c.100-4623C>T		intron	N/A	NP_066958.2
	RPS6KA2	NM_001318936.2		c.175-4623C>T		intron	N/A	NP_001305865.2
	RPS6KA2	NM_001006932.3		c.124-4623C>T		intron	N/A	NP_001006933.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	ENST00000265678.9	TSL:1 MANE Select	c.100-4623C>T		intron	N/A	ENSP00000265678.4
	RPS6KA2	ENST00000481261.6	TSL:1	c.-169+1193C>T		intron	N/A	ENSP00000422484.1
	RPS6KA2	ENST00000510118.5	TSL:2	c.175-4623C>T		intron	N/A	ENSP00000422435.1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60602 AN: 151888 Hom.: 12305 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.399 AC: 60679 AN: 152006 Hom.: 12333 Cov.: 32 AF XY: 0.403 AC XY: 29903 AN XY: 74290

African (AFR) AF: 0.315 AC: 13065 AN: 41462

American (AMR) AF: 0.471 AC: 7195 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1356 AN: 3468

East Asian (EAS) AF: 0.352 AC: 1821 AN: 5170

South Asian (SAS) AF: 0.561 AC: 2701 AN: 4818

European-Finnish (FIN) AF: 0.466 AC: 4918 AN: 10558

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28294 AN: 67938

Other (OTH) AF: 0.415 AC: 875 AN: 2110

Alfa AF: 0.411 Hom.: 55345

Bravo AF: 0.394

Asia WGS AF: 0.461 AC: 1604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.51
PhyloP100		-0.99
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: rs6918886; hg19: chr6-166956895;