NM_001318936.2:c.174+87578G>T

Variant names:

• chr6-166683285-C-A
• rs9295361
• NM_001318936.2:c.174+87578G>T

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+87578G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,144 control chromosomes in the GnomAD database, including 7,469 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 0.28 (7469 hom., cov: 33)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 9 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 (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_001318936.2	c.174+87578G>T		intron_variant	Intron 3 of 22		NP_001305865.2
RPS6KA2	NM_001006932.3	c.124-144501G>T		intron_variant	Intron 2 of 21		NP_001006933.3
RPS6KA2	NM_001318937.2	c.38-172961G>T		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+87578G>T		intron_variant	Intron 3 of 22	2		ENSP00000422435.1
RPS6KA2	ENST00000503859.5	c.124-144501G>T		intron_variant	Intron 2 of 21	2		ENSP00000427015.1
RPS6KA2	ENST00000714395.1	c.51+9508G>T		intron_variant	Intron 1 of 20			ENSP00000519662.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42739 AN: 152026 Hom.: 7447 Cov.: 33

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.281 AC: 42813 AN: 152144 Hom.: 7469 Cov.: 33 AF XY: 0.277 AC XY: 20586 AN XY: 74384

African (AFR) AF: 0.499 AC: 20694 AN: 41494

American (AMR) AF: 0.136 AC: 2073 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3468

East Asian (EAS) AF: 0.163 AC: 843 AN: 5176

South Asian (SAS) AF: 0.272 AC: 1313 AN: 4826

European-Finnish (FIN) AF: 0.219 AC: 2321 AN: 10578

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14109 AN: 67998

Other (OTH) AF: 0.241 AC: 507 AN: 2108

Alfa AF: 0.225 Hom.: 14354

Bravo AF: 0.282

Asia WGS AF: 0.255 AC: 888 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	0.55
DANN	Benign	0.27
PhyloP100		-0.19
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: rs9295361; hg19: chr6-167096773;