chr6-166693585-G-A

Position:

• chr6-166693585-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318936.2(RPS6KA2):​c.174+77278C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,062 control chromosomes in the GnomAD database, including 20,977 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 0.51 (20977 hom., cov: 32)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA2	NM_001006932.3	c.124-154801C>T		intron_variant			NP_001006933.3
RPS6KA2	NM_001318936.2	c.174+77278C>T		intron_variant			NP_001305865.2
RPS6KA2	NM_001318937.2	c.37+168523C>T		intron_variant			NP_001305866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000503859.5	c.124-154801C>T		intron_variant		2		ENSP00000427015
RPS6KA2	ENST00000506565.1	c.174+77278C>T		intron_variant		4		ENSP00000425148
RPS6KA2	ENST00000507371.5	c.51+63942C>T		intron_variant		3		ENSP00000423114

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77693 AN: 151944 Hom.: 20928 Cov.: 32

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.512 AC: 77798 AN: 152062 Hom.: 20977 Cov.: 32 AF XY: 0.505 AC XY: 37522 AN XY: 74312

Gnomad4 AFR AF: 0.691

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.512

Alfa AF: 0.501 Hom.: 3514

Bravo AF: 0.515

Asia WGS AF: 0.444 AC: 1546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.21
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7766723; hg19: chr6-167107073;