chr6-166771393-T-C

Variant names:

• chr6-166771393-T-C
• rs2345067
• NM_001318936.2:c.124-480A>G

Variant summary

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

The NM_001318936.2(RPS6KA2):​c.124-480A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 152,004 control chromosomes in the GnomAD database, including 22,505 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 0.53 (22505 hom., cov: 32)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_001318936.2	c.124-480A>G		intron_variant	Intron 2 of 22		NP_001305865.2
RPS6KA2	NM_001006932.3	c.123+86807A>G		intron_variant	Intron 2 of 21		NP_001006933.3
RPS6KA2	NM_001318937.2	c.37+90715A>G		intron_variant	Intron 1 of 18		NP_001305866.1
RPS6KA2	XM_047419235.1	c.-169+86807A>G		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.124-480A>G		intron_variant	Intron 2 of 22	2		ENSP00000422435.1
RPS6KA2	ENST00000503859.5	c.123+86807A>G		intron_variant	Intron 2 of 21	2		ENSP00000427015.1
RPS6KA2	ENST00000506565.1	c.124-480A>G		intron_variant	Intron 3 of 7	4		ENSP00000425148.1
RPS6KA2	ENST00000512860.5	c.-169+134965A>G		intron_variant	Intron 1 of 5	4		ENSP00000427605.1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80521 AN: 151886 Hom.: 22457 Cov.: 32

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.530 AC: 80626 AN: 152004 Hom.: 22505 Cov.: 32 AF XY: 0.533 AC XY: 39594 AN XY: 74298

African (AFR) AF: 0.676 AC: 28025 AN: 41468

American (AMR) AF: 0.535 AC: 8181 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2013 AN: 3470

East Asian (EAS) AF: 0.832 AC: 4298 AN: 5164

South Asian (SAS) AF: 0.581 AC: 2792 AN: 4808

European-Finnish (FIN) AF: 0.436 AC: 4599 AN: 10556

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.428 AC: 29063 AN: 67938

Other (OTH) AF: 0.519 AC: 1096 AN: 2110

Alfa AF: 0.471 Hom.: 51773

Bravo AF: 0.546

Asia WGS AF: 0.714 AC: 2480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.042
DANN	Benign	0.23
PhyloP100		-1.1
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: rs2345067; hg19: chr6-167184881; COSMIC: COSV72313043;