6-166774862-T-C

Variant names:

• chr6-166774862-T-C
• rs2072638
• NM_001318936.2:c.124-3949A>G

Variant summary

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

The NM_001318936.2(RPS6KA2):​c.124-3949A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 150,396 control chromosomes in the GnomAD database, including 9,686 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 0.35 (9686 hom., cov: 31)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.735
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	NM_001318936.2		c.124-3949A>G		intron	N/A	NP_001305865.2	F2Z2J1
	RPS6KA2	NM_001006932.3		c.123+83338A>G		intron	N/A	NP_001006933.3	Q15349-3
	RPS6KA2	NM_001318937.2		c.37+87246A>G		intron	N/A	NP_001305866.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	ENST00000510118.5	TSL:2	c.124-3949A>G		intron	N/A	ENSP00000422435.1	F2Z2J1
	RPS6KA2	ENST00000503859.5	TSL:2	c.123+83338A>G		intron	N/A	ENSP00000427015.1	Q15349-3
	RPS6KA2	ENST00000506565.1	TSL:4	c.124-3949A>G		intron	N/A	ENSP00000425148.1	D6RE03

Frequencies

GnomAD3 genomes AF: 0.350 AC: 52580 AN: 150282 Hom.: 9668 Cov.: 31

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.350 AC: 52634 AN: 150396 Hom.: 9686 Cov.: 31 AF XY: 0.350 AC XY: 25721 AN XY: 73542

African (AFR) AF: 0.374 AC: 14965 AN: 39968

American (AMR) AF: 0.301 AC: 4587 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1386 AN: 3440

East Asian (EAS) AF: 0.479 AC: 2468 AN: 5156

South Asian (SAS) AF: 0.374 AC: 1805 AN: 4822

European-Finnish (FIN) AF: 0.343 AC: 3626 AN: 10562

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.334 AC: 22658 AN: 67922

Other (OTH) AF: 0.340 AC: 715 AN: 2100

Alfa AF: 0.346 Hom.: 21791

Bravo AF: 0.347

Asia WGS AF: 0.442 AC: 1540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.66
DANN	Benign	0.67
PhyloP100		-0.73
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: rs2072638; hg19: chr6-167188350;