6-166718340-G-T

Variant names:

• chr6-166718340-G-T
• rs6456108
• NM_001318936.2:c.174+52523C>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.174+52523C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 152,188 control chromosomes in the GnomAD database, including 62,259 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 0.90 (62259 hom., cov: 31)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_001318936.2	c.174+52523C>A		intron_variant	Intron 3 of 22		NP_001305865.2
RPS6KA2	NM_001006932.3	c.123+139860C>A		intron_variant	Intron 2 of 21		NP_001006933.3
RPS6KA2	NM_001318937.2	c.37+143768C>A		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+52523C>A		intron_variant	Intron 3 of 22	2		ENSP00000422435.1
RPS6KA2	ENST00000503859.5	c.123+139860C>A		intron_variant	Intron 2 of 21	2		ENSP00000427015.1
RPS6KA2	ENST00000506565.1	c.174+52523C>A		intron_variant	Intron 4 of 7	4		ENSP00000425148.1

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137443 AN: 152070 Hom.: 62199 Cov.: 31

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.891

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.958

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.882

Gnomad OTH AF: 0.896

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

GnomAD4 genome AF: 0.904 AC: 137562 AN: 152188 Hom.: 62259 Cov.: 31 AF XY: 0.906 AC XY: 67396 AN XY: 74414

African (AFR) AF: 0.934 AC: 38768 AN: 41516

American (AMR) AF: 0.907 AC: 13867 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 3091 AN: 3468

East Asian (EAS) AF: 0.964 AC: 4995 AN: 5182

South Asian (SAS) AF: 0.959 AC: 4620 AN: 4818

European-Finnish (FIN) AF: 0.875 AC: 9283 AN: 10606

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.882 AC: 59955 AN: 67996

Other (OTH) AF: 0.896 AC: 1894 AN: 2114

Alfa AF: 0.894 Hom.: 30400

Bravo AF: 0.907

Asia WGS AF: 0.962 AC: 3345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.25
DANN	Benign	0.44
PhyloP100		-0.28
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: rs6456108; hg19: chr6-167131828;