rs661325

chr6-166767544-C-Gchr6-166767544-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA2	NM_001006932.3	c.123+90656G>C		intron_variant
RPS6KA2	NM_001318936.2	c.174+3319G>C		intron_variant
RPS6KA2	NM_001318937.2	c.37+94564G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA2	ENST00000503859.5	c.123+90656G>C		intron_variant		2
RPS6KA2	ENST00000506565.1	c.174+3319G>C		intron_variant		4
RPS6KA2	ENST00000510118.5	c.174+3319G>C		intron_variant		2
RPS6KA2	ENST00000512860.5	c.-169+138814G>C		intron_variant		4

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

Gnomad4 AFR AF: 0.899

Gnomad4 AMR AF: 0.698

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.861

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.707

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.723

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	2.3
Dann	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs661325; hg19: chr6-167181032;