rs2072641

Variant names:

• chr6-166775004-A-G
• rs2072641
• NM_001318936.2:c.124-4091T>C

Variant summary

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

The NM_001318936.2(RPS6KA2):​c.124-4091T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 151,812 control chromosomes in the GnomAD database, including 7,047 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 0.30 (7047 hom., cov: 31)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.632
• 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 = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_001318936.2	c.124-4091T>C		intron_variant	Intron 2 of 22		NP_001305865.2
RPS6KA2	NM_001006932.3	c.123+83196T>C		intron_variant	Intron 2 of 21		NP_001006933.3
RPS6KA2	NM_001318937.2	c.37+87104T>C		intron_variant	Intron 1 of 18		NP_001305866.1
RPS6KA2	XM_047419235.1	c.-169+83196T>C		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.124-4091T>C		intron_variant	Intron 2 of 22	2		ENSP00000422435.1
RPS6KA2	ENST00000503859.5	c.123+83196T>C		intron_variant	Intron 2 of 21	2		ENSP00000427015.1
RPS6KA2	ENST00000506565.1	c.124-4091T>C		intron_variant	Intron 3 of 7	4		ENSP00000425148.1
RPS6KA2	ENST00000512860.5	c.-169+131354T>C		intron_variant	Intron 1 of 5	4		ENSP00000427605.1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45158 AN: 151694 Hom.: 7032 Cov.: 31

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.298 AC: 45205 AN: 151812 Hom.: 7047 Cov.: 31 AF XY: 0.299 AC XY: 22205 AN XY: 74196

African (AFR) AF: 0.367 AC: 15151 AN: 41276

American (AMR) AF: 0.253 AC: 3863 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1240 AN: 3464

East Asian (EAS) AF: 0.510 AC: 2628 AN: 5156

South Asian (SAS) AF: 0.368 AC: 1774 AN: 4816

European-Finnish (FIN) AF: 0.255 AC: 2688 AN: 10560

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16860 AN: 67960

Other (OTH) AF: 0.292 AC: 615 AN: 2106

Alfa AF: 0.268 Hom.: 9606

Bravo AF: 0.302

Asia WGS AF: 0.447 AC: 1554 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	1.7
DANN	Benign	0.76
PhyloP100		0.63
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: rs2072641; hg19: chr6-167188492; COSMIC: COSV72313656;