rs932356

Variant names:

• chr6-166684947-G-C
• rs932356
• NM_001318936.2:c.174+85916C>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.174+85916C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,236 control chromosomes in the GnomAD database, including 2,079 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 0.16 (2079 hom., cov: 33)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.773
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_001318936.2	c.174+85916C>G		intron_variant	Intron 3 of 22		NP_001305865.2
RPS6KA2	NM_001006932.3	c.124-146163C>G		intron_variant	Intron 2 of 21		NP_001006933.3
RPS6KA2	NM_001318937.2	c.38-174623C>G		intron_variant	Intron 1 of 18		NP_001305866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000510118.5	c.174+85916C>G		intron_variant	Intron 3 of 22	2		ENSP00000422435.1
RPS6KA2	ENST00000503859.5	c.124-146163C>G		intron_variant	Intron 2 of 21	2		ENSP00000427015.1
RPS6KA2	ENST00000714395.1	c.51+7846C>G		intron_variant	Intron 1 of 20			ENSP00000519662.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24012 AN: 152118 Hom.: 2073 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.158 AC: 24026 AN: 152236 Hom.: 2079 Cov.: 33 AF XY: 0.156 AC XY: 11608 AN XY: 74438

African (AFR) AF: 0.111 AC: 4613 AN: 41554

American (AMR) AF: 0.139 AC: 2130 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 727 AN: 3472

East Asian (EAS) AF: 0.272 AC: 1408 AN: 5174

South Asian (SAS) AF: 0.174 AC: 841 AN: 4820

European-Finnish (FIN) AF: 0.123 AC: 1309 AN: 10604

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12392 AN: 67996

Other (OTH) AF: 0.173 AC: 365 AN: 2108

Alfa AF: 0.168 Hom.: 282

Bravo AF: 0.156

Asia WGS AF: 0.213 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.2
DANN	Benign	0.67
PhyloP100		0.77
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: rs932356; hg19: chr6-167098435;