chr6-166670202-A-G

Position:

• chr6-166670202-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318936.2(RPS6KA2):​c.174+100661T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 152,180 control chromosomes in the GnomAD database, including 17,632 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 0.47 (17632 hom., cov: 33)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA2	NM_001006932.3	c.124-131418T>C		intron_variant			NP_001006933.3
RPS6KA2	NM_001318936.2	c.174+100661T>C		intron_variant			NP_001305865.2
RPS6KA2	NM_001318937.2	c.38-159878T>C		intron_variant			NP_001305866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000503859.5	c.124-131418T>C		intron_variant		2		ENSP00000427015
RPS6KA2	ENST00000506565.1	c.174+100661T>C		intron_variant		4		ENSP00000425148
RPS6KA2	ENST00000507371.5	c.51+87325T>C		intron_variant		3		ENSP00000423114

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72165 AN: 152062 Hom.: 17584 Cov.: 33

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.475 AC: 72273 AN: 152180 Hom.: 17632 Cov.: 33 AF XY: 0.471 AC XY: 35078 AN XY: 74414

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.477

Alfa AF: 0.447 Hom.: 30908

Bravo AF: 0.475

Asia WGS AF: 0.472 AC: 1641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6921577; hg19: chr6-167083690;