6-166775004-A-G

Position:

• chr6-166775004-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
RPS6KA2	NM_001006932.3	c.123+83196T>C		intron_variant			NP_001006933.3
RPS6KA2	NM_001318936.2	c.124-4091T>C		intron_variant			NP_001305865.2
RPS6KA2	NM_001318937.2	c.37+87104T>C		intron_variant			NP_001305866.1
RPS6KA2	XM_047419235.1	c.-169+83196T>C		intron_variant			XP_047275191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000503859.5	c.123+83196T>C		intron_variant		2		ENSP00000427015
RPS6KA2	ENST00000506565.1	c.124-4091T>C		intron_variant		4		ENSP00000425148
RPS6KA2	ENST00000510118.5	c.124-4091T>C		intron_variant		2		ENSP00000422435
RPS6KA2	ENST00000512860.5	c.-169+131354T>C		intron_variant		4		ENSP00000427605

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

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.292

Alfa AF: 0.264 Hom.: 7407

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2072641; hg19: chr6-167188492; COSMIC: COSV72313656;