6-166413532-A-G

Variant names:

• chr6-166413532-A-G
• rs2235296
• NM_021135.6:c.2076+262T>C

Variant summary

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

The NM_021135.6(RPS6KA2):​c.2076+262T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 152,028 control chromosomes in the GnomAD database, including 36,750 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 0.69 (36750 hom., cov: 31)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.622
• Publications: 8 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]

LOC124901460 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.82 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.2076+262T>C		intron	N/A	NP_066958.2
	RPS6KA2	NM_001318936.2		c.2151+262T>C		intron	N/A	NP_001305865.2	F2Z2J1
	RPS6KA2	NM_001006932.3		c.2100+262T>C		intron	N/A	NP_001006933.3	Q15349-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	ENST00000265678.9	TSL:1 MANE Select	c.2076+262T>C		intron	N/A	ENSP00000265678.4	Q15349-1
	RPS6KA2	ENST00000481261.6	TSL:1	c.1809+262T>C		intron	N/A	ENSP00000422484.1	B7Z3B5
	RPS6KA2	ENST00000509742.1	TSL:1	n.612+262T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105171 AN: 151910 Hom.: 36700 Cov.: 31

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.693 AC: 105281 AN: 152028 Hom.: 36750 Cov.: 31 AF XY: 0.691 AC XY: 51363 AN XY: 74304

African (AFR) AF: 0.711 AC: 29485 AN: 41470

American (AMR) AF: 0.730 AC: 11158 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2618 AN: 3466

East Asian (EAS) AF: 0.814 AC: 4192 AN: 5152

South Asian (SAS) AF: 0.842 AC: 4046 AN: 4806

European-Finnish (FIN) AF: 0.573 AC: 6055 AN: 10570

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.668 AC: 45436 AN: 67970

Other (OTH) AF: 0.728 AC: 1539 AN: 2114

Alfa AF: 0.680 Hom.: 6112

Bravo AF: 0.703

Asia WGS AF: 0.810 AC: 2816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.015
DANN	Benign	0.64
PhyloP100		-0.62
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: rs2235296; hg19: chr6-166827020;