rs13198549

Variant names:

• chr6-166760209-G-A
• rs13198549
• NM_001318936.2:c.174+10654C>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+10654C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,058 control chromosomes in the GnomAD database, including 24,801 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 0.56 (24801 hom., cov: 33)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_001318936.2	c.174+10654C>T		intron_variant	Intron 3 of 22		NP_001305865.2
RPS6KA2	NM_001006932.3	c.123+97991C>T		intron_variant	Intron 2 of 21		NP_001006933.3
RPS6KA2	NM_001318937.2	c.37+101899C>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+10654C>T		intron_variant	Intron 3 of 22	2		ENSP00000422435.1
RPS6KA2	ENST00000503859.5	c.123+97991C>T		intron_variant	Intron 2 of 21	2		ENSP00000427015.1
RPS6KA2	ENST00000506565.1	c.174+10654C>T		intron_variant	Intron 4 of 7	4		ENSP00000425148.1
RPS6KA2	ENST00000512860.5	c.-169+146149C>T		intron_variant	Intron 1 of 5	4		ENSP00000427605.1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 85003 AN: 151940 Hom.: 24790 Cov.: 33

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.559 AC: 85064 AN: 152058 Hom.: 24801 Cov.: 33 AF XY: 0.561 AC XY: 41668 AN XY: 74298

African (AFR) AF: 0.378 AC: 15684 AN: 41482

American (AMR) AF: 0.583 AC: 8909 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2263 AN: 3468

East Asian (EAS) AF: 0.709 AC: 3666 AN: 5172

South Asian (SAS) AF: 0.693 AC: 3342 AN: 4822

European-Finnish (FIN) AF: 0.603 AC: 6361 AN: 10546

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42833 AN: 67962

Other (OTH) AF: 0.581 AC: 1228 AN: 2114

Alfa AF: 0.599 Hom.: 5630

Bravo AF: 0.549

Asia WGS AF: 0.617 AC: 2143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.9
DANN	Benign	0.84
PhyloP100		0.37
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: rs13198549; hg19: chr6-167173697; COSMIC: COSV72313029; COSMIC: COSV72313029;