6-166774862-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_001318936.2	c.124-3949A>G		intron_variant	Intron 2 of 22		NP_001305865.2
RPS6KA2	NM_001006932.3	c.123+83338A>G		intron_variant	Intron 2 of 21		NP_001006933.3
RPS6KA2	NM_001318937.2	c.37+87246A>G		intron_variant	Intron 1 of 18		NP_001305866.1
RPS6KA2	XM_047419235.1	c.-169+83338A>G		intron_variant	Intron 2 of 21		XP_047275191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000510118.5	c.124-3949A>G		intron_variant	Intron 2 of 22	2		ENSP00000422435.1
RPS6KA2	ENST00000503859.5	c.123+83338A>G		intron_variant	Intron 2 of 21	2		ENSP00000427015.1
RPS6KA2	ENST00000506565.1	c.124-3949A>G		intron_variant	Intron 3 of 7	4		ENSP00000425148.1
RPS6KA2	ENST00000512860.5	c.-169+131496A>G		intron_variant	Intron 1 of 5	4		ENSP00000427605.1

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

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.340

Alfa AF: 0.342 Hom.: 14983

Bravo AF: 0.347

Asia WGS AF: 0.442 AC: 1540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.66
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2072638; hg19: chr6-167188350;