chr6-166670202-A-G

Variant names:

• chr6-166670202-A-G
• rs6921577
• NM_001318936.2:c.174+100661T>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+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
• 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]

ENSG00000301701 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	NM_001318936.2		c.174+100661T>C		intron	N/A	NP_001305865.2
	RPS6KA2	NM_001006932.3		c.124-131418T>C		intron	N/A	NP_001006933.3
	RPS6KA2	NM_001318937.2		c.38-159878T>C		intron	N/A	NP_001305866.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	ENST00000510118.5	TSL:2	c.174+100661T>C		intron	N/A	ENSP00000422435.1
	RPS6KA2	ENST00000503859.5	TSL:2	c.124-131418T>C		intron	N/A	ENSP00000427015.1
	RPS6KA2	ENST00000714395.1		c.51+22591T>C		intron	N/A	ENSP00000519662.1

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

African (AFR) AF: 0.583 AC: 24210 AN: 41534

American (AMR) AF: 0.407 AC: 6225 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1680 AN: 3470

East Asian (EAS) AF: 0.372 AC: 1923 AN: 5174

South Asian (SAS) AF: 0.477 AC: 2298 AN: 4820

European-Finnish (FIN) AF: 0.393 AC: 4163 AN: 10590

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30199 AN: 67980

Other (OTH) AF: 0.477 AC: 1009 AN: 2114

Alfa AF: 0.453 Hom.: 67505

Bravo AF: 0.475

Asia WGS AF: 0.472 AC: 1641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.47
PhyloP100		-0.72
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: rs6921577; hg19: chr6-167083690;