6-166767544-C-G

Variant names:

• chr6-166767544-C-G
• rs661325
• NM_001318936.2:c.174+3319G>C

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+3319G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 151,952 control chromosomes in the GnomAD database, including 41,605 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 0.73 (41605 hom., cov: 30)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 4 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 = 0.892 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318936.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	NM_001318936.2		c.174+3319G>C		intron	N/A	NP_001305865.2	F2Z2J1
	RPS6KA2	NM_001006932.3		c.123+90656G>C		intron	N/A	NP_001006933.3	Q15349-3
	RPS6KA2	NM_001318937.2		c.37+94564G>C		intron	N/A	NP_001305866.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	ENST00000510118.5	TSL:2	c.174+3319G>C		intron	N/A	ENSP00000422435.1	F2Z2J1
	RPS6KA2	ENST00000503859.5	TSL:2	c.123+90656G>C		intron	N/A	ENSP00000427015.1	Q15349-3
	RPS6KA2	ENST00000506565.1	TSL:4	c.174+3319G>C		intron	N/A	ENSP00000425148.1	D6RE03

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110909 AN: 151834 Hom.: 41542 Cov.: 30

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.860

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.721

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

GnomAD4 genome AF: 0.731 AC: 111033 AN: 151952 Hom.: 41605 Cov.: 30 AF XY: 0.731 AC XY: 54295 AN XY: 74252

African (AFR) AF: 0.899 AC: 37272 AN: 41444

American (AMR) AF: 0.698 AC: 10655 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 2455 AN: 3468

East Asian (EAS) AF: 0.861 AC: 4420 AN: 5136

South Asian (SAS) AF: 0.603 AC: 2906 AN: 4816

European-Finnish (FIN) AF: 0.707 AC: 7460 AN: 10548

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.640 AC: 43523 AN: 67968

Other (OTH) AF: 0.723 AC: 1518 AN: 2100

Alfa AF: 0.700 Hom.: 4701

Bravo AF: 0.737

Asia WGS AF: 0.741 AC: 2575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.3
DANN	Benign	0.51
PhyloP100		-1.1
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: rs661325; hg19: chr6-167181032;