6-166491713-C-T

Variant names:

• chr6-166491713-C-T
• rs3817782
• NM_021135.6:c.748-972G>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.748-972G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 151,958 control chromosomes in the GnomAD database, including 22,060 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 0.52 (22060 hom., cov: 32)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_021135.6	c.748-972G>A		intron_variant	Intron 8 of 20	ENST00000265678.9	NP_066958.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000265678.9	c.748-972G>A		intron_variant	Intron 8 of 20	1	NM_021135.6	ENSP00000265678.4

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79383 AN: 151840 Hom.: 22015 Cov.: 32

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.523 AC: 79487 AN: 151958 Hom.: 22060 Cov.: 32 AF XY: 0.525 AC XY: 38973 AN XY: 74256

African (AFR) AF: 0.701 AC: 29045 AN: 41450

American (AMR) AF: 0.568 AC: 8670 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1247 AN: 3466

East Asian (EAS) AF: 0.634 AC: 3270 AN: 5156

South Asian (SAS) AF: 0.536 AC: 2587 AN: 4828

European-Finnish (FIN) AF: 0.468 AC: 4930 AN: 10530

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28146 AN: 67948

Other (OTH) AF: 0.499 AC: 1050 AN: 2106

Alfa AF: 0.433 Hom.: 9287

Bravo AF: 0.540

Asia WGS AF: 0.580 AC: 2016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.70
DANN	Benign	0.55
PhyloP100		-0.55
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: rs3817782; hg19: chr6-166905201;