NM_001318936.2:c.123+41591G>A

Variant names:

• chr6-166816609-C-T
• rs1309150
• NM_001318936.2:c.123+41591G>A

Variant summary

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

The NM_001318936.2(RPS6KA2):​c.123+41591G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 151,708 control chromosomes in the GnomAD database, including 41,013 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 0.73 (41013 hom., cov: 30)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_001318936.2	c.123+41591G>A		intron_variant	Intron 2 of 22		NP_001305865.2
RPS6KA2	NM_001006932.3	c.123+41591G>A		intron_variant	Intron 2 of 21		NP_001006933.3
RPS6KA2	NM_001318937.2	c.37+45499G>A		intron_variant	Intron 1 of 18		NP_001305866.1
RPS6KA2	XM_047419235.1	c.-169+41591G>A		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+41591G>A		intron_variant	Intron 2 of 22	2		ENSP00000422435.1
RPS6KA2	ENST00000503859.5	c.123+41591G>A		intron_variant	Intron 2 of 21	2		ENSP00000427015.1
RPS6KA2	ENST00000506565.1	c.123+41591G>A		intron_variant	Intron 3 of 7	4		ENSP00000425148.1
RPS6KA2	ENST00000512860.5	c.-169+89749G>A		intron_variant	Intron 1 of 5	4		ENSP00000427605.1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111111 AN: 151596 Hom.: 40992 Cov.: 30

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.733 AC: 111178 AN: 151708 Hom.: 41013 Cov.: 30 AF XY: 0.736 AC XY: 54539 AN XY: 74136

African (AFR) AF: 0.651 AC: 26876 AN: 41284

American (AMR) AF: 0.751 AC: 11459 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2349 AN: 3464

East Asian (EAS) AF: 0.925 AC: 4787 AN: 5176

South Asian (SAS) AF: 0.818 AC: 3935 AN: 4812

European-Finnish (FIN) AF: 0.735 AC: 7695 AN: 10466

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.759 AC: 51571 AN: 67928

Other (OTH) AF: 0.755 AC: 1592 AN: 2110

Alfa AF: 0.749 Hom.: 61284

Bravo AF: 0.730

Asia WGS AF: 0.835 AC: 2906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.14
DANN	Benign	0.65
PhyloP100		-1.6
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: rs1309150; hg19: chr6-167230097;