chr6-166850818-C-T

Position:

• chr6-166850818-C-T

Variant summary

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

The NM_001318936.2(RPS6KA2):​c.123+7382G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 151,896 control chromosomes in the GnomAD database, including 26,890 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 0.55 (26890 hom., cov: 30)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.684

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA2	NM_001006932.3	c.123+7382G>A		intron_variant			NP_001006933.3
RPS6KA2	NM_001318936.2	c.123+7382G>A		intron_variant			NP_001305865.2
RPS6KA2	NM_001318937.2	c.37+11290G>A		intron_variant			NP_001305866.1
RPS6KA2	XM_047419235.1	c.-169+7382G>A		intron_variant			XP_047275191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000503859.5	c.123+7382G>A		intron_variant		2		ENSP00000427015
RPS6KA2	ENST00000506565.1	c.123+7382G>A		intron_variant		4		ENSP00000425148
RPS6KA2	ENST00000510118.5	c.123+7382G>A		intron_variant		2		ENSP00000422435
RPS6KA2	ENST00000512860.5	c.-169+55540G>A		intron_variant		4		ENSP00000427605

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84158 AN: 151778 Hom.: 26897 Cov.: 30

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.554 AC: 84162 AN: 151896 Hom.: 26890 Cov.: 30 AF XY: 0.551 AC XY: 40889 AN XY: 74222

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.634

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.720

Gnomad4 OTH AF: 0.600

Alfa AF: 0.641 Hom.: 9742

Bravo AF: 0.539

Asia WGS AF: 0.405 AC: 1410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9348195; hg19: chr6-167264306;