rs388372

Positions:

• chr6-166763446-T-C
• chr6-166763446-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318936.2(RPS6KA2):​c.174+7417A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 152,102 control chromosomes in the GnomAD database, including 36,505 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 0.68 (36505 hom., cov: 32)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA2	NM_001006932.3	c.123+94754A>G		intron_variant			NP_001006933.3
RPS6KA2	NM_001318936.2	c.174+7417A>G		intron_variant			NP_001305865.2
RPS6KA2	NM_001318937.2	c.37+98662A>G		intron_variant			NP_001305866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000503859.5	c.123+94754A>G		intron_variant		2		ENSP00000427015
RPS6KA2	ENST00000506565.1	c.174+7417A>G		intron_variant		4		ENSP00000425148
RPS6KA2	ENST00000510118.5	c.174+7417A>G		intron_variant		2		ENSP00000422435
RPS6KA2	ENST00000512860.5	c.-169+142912A>G		intron_variant		4		ENSP00000427605

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104042 AN: 151984 Hom.: 36440 Cov.: 32

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.685 AC: 104173 AN: 152102 Hom.: 36505 Cov.: 32 AF XY: 0.682 AC XY: 50713 AN XY: 74366

Gnomad4 AFR AF: 0.843

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.623

Gnomad4 OTH AF: 0.676

Alfa AF: 0.630 Hom.: 43336

Bravo AF: 0.696

Asia WGS AF: 0.635 AC: 2207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.2
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs388372; hg19: chr6-167176934;