chr6-166801198-G-A

Variant names:

• chr6-166801198-G-A
• rs10484520
• NM_001318936.2:c.124-30285C>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.124-30285C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0426 in 152,164 control chromosomes in the GnomAD database, including 545 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 0.043 (545 hom., cov: 33)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 6 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]

LOC124901459 (HGNC:):

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 = 0.376 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318936.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	NM_001318936.2		c.124-30285C>T		intron	N/A	NP_001305865.2	F2Z2J1
	RPS6KA2	NM_001006932.3		c.123+57002C>T		intron	N/A	NP_001006933.3	Q15349-3
	RPS6KA2	NM_001318937.2		c.37+60910C>T		intron	N/A	NP_001305866.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	ENST00000510118.5	TSL:2	c.124-30285C>T		intron	N/A	ENSP00000422435.1	F2Z2J1
	RPS6KA2	ENST00000503859.5	TSL:2	c.123+57002C>T		intron	N/A	ENSP00000427015.1	Q15349-3
	RPS6KA2	ENST00000506565.1	TSL:4	c.124-30285C>T		intron	N/A	ENSP00000425148.1	D6RE03

Frequencies

GnomAD3 genomes AF: 0.0426 AC: 6480 AN: 152046 Hom.: 544 Cov.: 33

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0690

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0785

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0201

Gnomad OTH AF: 0.0353

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

GnomAD4 genome AF: 0.0426 AC: 6486 AN: 152164 Hom.: 545 Cov.: 33 AF XY: 0.0483 AC XY: 3594 AN XY: 74412

African (AFR) AF: 0.0124 AC: 515 AN: 41494

American (AMR) AF: 0.0693 AC: 1060 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3468

East Asian (EAS) AF: 0.390 AC: 2019 AN: 5180

South Asian (SAS) AF: 0.117 AC: 563 AN: 4818

European-Finnish (FIN) AF: 0.0785 AC: 831 AN: 10582

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0201 AC: 1366 AN: 68002

Other (OTH) AF: 0.0373 AC: 79 AN: 2116

Alfa AF: 0.0364 Hom.: 44

Bravo AF: 0.0429

Asia WGS AF: 0.267 AC: 926 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.67
PhyloP100		-1.0
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: rs10484520; hg19: chr6-167214686;