6-166466806-A-T

Variant names:

• chr6-166466806-A-T
• rs12200581
• NM_021135.6:c.972+3035T>A

Variant summary

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

The NM_021135.6(RPS6KA2):​c.972+3035T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 151,750 control chromosomes in the GnomAD database, including 1,836 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 0.14 (1836 hom., cov: 33)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.534
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_021135.6	c.972+3035T>A		intron_variant	Intron 11 of 20	ENST00000265678.9	NP_066958.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000265678.9	c.972+3035T>A		intron_variant	Intron 11 of 20	1	NM_021135.6	ENSP00000265678.4

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20550 AN: 151632 Hom.: 1836 Cov.: 33

Gnomad AFR AF: 0.0369

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0392

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.135 AC: 20549 AN: 151750 Hom.: 1836 Cov.: 33 AF XY: 0.130 AC XY: 9624 AN XY: 74138

African (AFR) AF: 0.0368 AC: 1521 AN: 41332

American (AMR) AF: 0.113 AC: 1730 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 749 AN: 3468

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5180

South Asian (SAS) AF: 0.0394 AC: 189 AN: 4796

European-Finnish (FIN) AF: 0.164 AC: 1718 AN: 10506

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14156 AN: 67892

Other (OTH) AF: 0.131 AC: 276 AN: 2104

Alfa AF: 0.0933 Hom.: 146

Bravo AF: 0.129

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.54
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs12200581; hg19: chr6-166880294;