rs1927430

Variant names:

• chr6-166787325-A-G
• rs1927430
• NM_001318936.2:c.124-16412T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318936.2(RPS6KA2):​c.124-16412T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,968 control chromosomes in the GnomAD database, including 9,886 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 0.35 (9886 hom., cov: 33)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220
• Publications: 5 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=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_001318936.2	c.124-16412T>C		intron_variant	Intron 2 of 22		NP_001305865.2
RPS6KA2	NM_001006932.3	c.123+70875T>C		intron_variant	Intron 2 of 21		NP_001006933.3
RPS6KA2	NM_001318937.2	c.37+74783T>C		intron_variant	Intron 1 of 18		NP_001305866.1
RPS6KA2	XM_047419235.1	c.-169+70875T>C		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.124-16412T>C		intron_variant	Intron 2 of 22	2		ENSP00000422435.1
RPS6KA2	ENST00000503859.5	c.123+70875T>C		intron_variant	Intron 2 of 21	2		ENSP00000427015.1
RPS6KA2	ENST00000506565.1	c.124-16412T>C		intron_variant	Intron 3 of 7	4		ENSP00000425148.1
RPS6KA2	ENST00000512860.5	c.-169+119033T>C		intron_variant	Intron 1 of 5	4		ENSP00000427605.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52744 AN: 151850 Hom.: 9862 Cov.: 33

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.0516

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.348 AC: 52809 AN: 151968 Hom.: 9886 Cov.: 33 AF XY: 0.341 AC XY: 25339 AN XY: 74270

African (AFR) AF: 0.472 AC: 19555 AN: 41430

American (AMR) AF: 0.283 AC: 4321 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1174 AN: 3470

East Asian (EAS) AF: 0.0514 AC: 266 AN: 5180

South Asian (SAS) AF: 0.252 AC: 1216 AN: 4818

European-Finnish (FIN) AF: 0.290 AC: 3056 AN: 10524

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22221 AN: 67948

Other (OTH) AF: 0.349 AC: 737 AN: 2110

Alfa AF: 0.330 Hom.: 30873

Bravo AF: 0.351

Asia WGS AF: 0.173 AC: 595 AN: 3428

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.0
DANN	Benign	0.87
PhyloP100		0.022
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: rs1927430; hg19: chr6-167200813;