NM_001318936.2:c.123+549C>T

Variant names:

• chr6-166857651-G-A
• rs9356529
• NM_001318936.2:c.123+549C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318936.2(RPS6KA2):​c.123+549C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 152,066 control chromosomes in the GnomAD database, including 29,223 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 0.58 (29223 hom., cov: 32)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_001318936.2	c.123+549C>T		intron_variant	Intron 2 of 22		NP_001305865.2
RPS6KA2	NM_001006932.3	c.123+549C>T		intron_variant	Intron 2 of 21		NP_001006933.3
RPS6KA2	NM_001318937.2	c.37+4457C>T		intron_variant	Intron 1 of 18		NP_001305866.1
RPS6KA2	XM_047419235.1	c.-169+549C>T		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+549C>T		intron_variant	Intron 2 of 22	2		ENSP00000422435.1
RPS6KA2	ENST00000503859.5	c.123+549C>T		intron_variant	Intron 2 of 21	2		ENSP00000427015.1
RPS6KA2	ENST00000506565.1	c.123+549C>T		intron_variant	Intron 3 of 7	4		ENSP00000425148.1
RPS6KA2	ENST00000512860.5	c.-169+48707C>T		intron_variant	Intron 1 of 5	4		ENSP00000427605.1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87829 AN: 151948 Hom.: 29223 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.611

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

GnomAD4 genome AF: 0.578 AC: 87832 AN: 152066 Hom.: 29223 Cov.: 32 AF XY: 0.578 AC XY: 43002 AN XY: 74336

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.740

Gnomad4 OTH AF: 0.609

Alfa AF: 0.712 Hom.: 78906

Bravo AF: 0.559

Asia WGS AF: 0.564 AC: 1964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.32
DANN	Benign	0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9356529; hg19: chr6-167271139;