6-166509806-G-A

Variant names:

• chr6-166509806-G-A
• rs395475
• NM_021135.6:c.379+471C>T

Variant summary

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

The NM_021135.6(RPS6KA2):​c.379+471C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 152,050 control chromosomes in the GnomAD database, including 20,045 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 0.50 (20045 hom., cov: 32)
• Consequence: RPS6KA2 NM_021135.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637
• 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 (SAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021135.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	NM_021135.6	MANE Select	c.379+471C>T		intron	N/A	NP_066958.2
	RPS6KA2	NM_001318936.2		c.454+471C>T		intron	N/A	NP_001305865.2
	RPS6KA2	NM_001006932.3		c.403+471C>T		intron	N/A	NP_001006933.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	ENST00000265678.9	TSL:1 MANE Select	c.379+471C>T		intron	N/A	ENSP00000265678.4
	RPS6KA2	ENST00000481261.6	TSL:1	c.112+471C>T		intron	N/A	ENSP00000422484.1
	RPS6KA2	ENST00000510118.5	TSL:2	c.454+471C>T		intron	N/A	ENSP00000422435.1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75563 AN: 151932 Hom.: 20002 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.498 AC: 75661 AN: 152050 Hom.: 20045 Cov.: 32 AF XY: 0.502 AC XY: 37311 AN XY: 74316

African (AFR) AF: 0.309 AC: 12807 AN: 41444

American (AMR) AF: 0.565 AC: 8634 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1904 AN: 3470

East Asian (EAS) AF: 0.452 AC: 2343 AN: 5184

South Asian (SAS) AF: 0.571 AC: 2752 AN: 4820

European-Finnish (FIN) AF: 0.675 AC: 7134 AN: 10564

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38409 AN: 67968

Other (OTH) AF: 0.527 AC: 1114 AN: 2114

Alfa AF: 0.530 Hom.: 17433

Bravo AF: 0.483

Asia WGS AF: 0.513 AC: 1786 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.26
DANN	Benign	0.32
PhyloP100		-0.64
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: rs395475; hg19: chr6-166923294; COSMIC: COSV55817571; COSMIC: COSV55817571;