6-166761908-C-T

Variant names:

• chr6-166761908-C-T
• rs505982
• NM_001318936.2:c.174+8955G>A

Variant summary

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

The NM_001318936.2(RPS6KA2):​c.174+8955G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 152,058 control chromosomes in the GnomAD database, including 15,544 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 0.42 (15544 hom., cov: 33)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_001318936.2	c.174+8955G>A		intron_variant	Intron 3 of 22		NP_001305865.2
RPS6KA2	NM_001006932.3	c.123+96292G>A		intron_variant	Intron 2 of 21		NP_001006933.3
RPS6KA2	NM_001318937.2	c.37+100200G>A		intron_variant	Intron 1 of 18		NP_001305866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000510118.5	c.174+8955G>A		intron_variant	Intron 3 of 22	2		ENSP00000422435.1
RPS6KA2	ENST00000503859.5	c.123+96292G>A		intron_variant	Intron 2 of 21	2		ENSP00000427015.1
RPS6KA2	ENST00000506565.1	c.174+8955G>A		intron_variant	Intron 4 of 7	4		ENSP00000425148.1
RPS6KA2	ENST00000512860.5	c.-169+144450G>A		intron_variant	Intron 1 of 5	4		ENSP00000427605.1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63978 AN: 151940 Hom.: 15511 Cov.: 33

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.421 AC: 64064 AN: 152058 Hom.: 15544 Cov.: 33 AF XY: 0.418 AC XY: 31085 AN XY: 74328

African (AFR) AF: 0.677 AC: 28070 AN: 41460

American (AMR) AF: 0.358 AC: 5473 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1042 AN: 3472

East Asian (EAS) AF: 0.245 AC: 1270 AN: 5174

South Asian (SAS) AF: 0.226 AC: 1088 AN: 4818

European-Finnish (FIN) AF: 0.357 AC: 3779 AN: 10578

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22055 AN: 67966

Other (OTH) AF: 0.397 AC: 836 AN: 2108

Alfa AF: 0.356 Hom.: 13091

Bravo AF: 0.436

Asia WGS AF: 0.316 AC: 1098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.29
DANN	Benign	0.51
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs505982; hg19: chr6-167175396; COSMIC: COSV72315863; COSMIC: COSV72315863;