6-166850818-C-T

Variant names:

• chr6-166850818-C-T
• rs9348195
• NM_001318936.2:c.123+7382G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.85).
• 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 rank	MANE	Protein	UniProt
RPS6KA2	NM_001318936.2	c.123+7382G>A		intron_variant	Intron 2 of 22		NP_001305865.2
RPS6KA2	NM_001006932.3	c.123+7382G>A		intron_variant	Intron 2 of 21		NP_001006933.3
RPS6KA2	NM_001318937.2	c.37+11290G>A		intron_variant	Intron 1 of 18		NP_001305866.1
RPS6KA2	XM_047419235.1	c.-169+7382G>A		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.123+7382G>A		intron_variant	Intron 2 of 22	2		ENSP00000422435.1
RPS6KA2	ENST00000503859.5	c.123+7382G>A		intron_variant	Intron 2 of 21	2		ENSP00000427015.1
RPS6KA2	ENST00000506565.1	c.123+7382G>A		intron_variant	Intron 3 of 7	4		ENSP00000425148.1
RPS6KA2	ENST00000512860.5	c.-169+55540G>A		intron_variant	Intron 1 of 5	4		ENSP00000427605.1

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

African (AFR) AF: 0.231 AC: 9545 AN: 41404

American (AMR) AF: 0.634 AC: 9691 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2709 AN: 3470

East Asian (EAS) AF: 0.334 AC: 1725 AN: 5160

South Asian (SAS) AF: 0.527 AC: 2519 AN: 4780

European-Finnish (FIN) AF: 0.660 AC: 6957 AN: 10548

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48920 AN: 67948

Other (OTH) AF: 0.600 AC: 1264 AN: 2106

Alfa AF: 0.646 Hom.: 14793

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
PhyloP100		-0.68
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: rs9348195; hg19: chr6-167264306;