rs880900

Variant names:

• chr6-166725991-A-G
• rs880900
• NM_001318936.2:c.174+44872T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-166725991-A-G
• chr6-166725991-A-T

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+44872T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,094 control chromosomes in the GnomAD database, including 13,463 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 0.37 (13463 hom., cov: 33)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.872
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 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+44872T>C		intron	N/A	NP_001305865.2
	RPS6KA2	NM_001006932.3		c.123+132209T>C		intron	N/A	NP_001006933.3
	RPS6KA2	NM_001318937.2		c.37+136117T>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+44872T>C		intron	N/A	ENSP00000422435.1
	RPS6KA2	ENST00000503859.5	TSL:2	c.123+132209T>C		intron	N/A	ENSP00000427015.1
	RPS6KA2	ENST00000506565.1	TSL:4	c.174+44872T>C		intron	N/A	ENSP00000425148.1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55788 AN: 151976 Hom.: 13417 Cov.: 33

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.367 AC: 55894 AN: 152094 Hom.: 13463 Cov.: 33 AF XY: 0.365 AC XY: 27141 AN XY: 74356

African (AFR) AF: 0.699 AC: 28998 AN: 41466

American (AMR) AF: 0.289 AC: 4428 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1299 AN: 3470

East Asian (EAS) AF: 0.244 AC: 1261 AN: 5162

South Asian (SAS) AF: 0.167 AC: 806 AN: 4824

European-Finnish (FIN) AF: 0.242 AC: 2561 AN: 10576

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15464 AN: 67984

Other (OTH) AF: 0.333 AC: 703 AN: 2110

Alfa AF: 0.280 Hom.: 20142

Bravo AF: 0.387

Asia WGS AF: 0.243 AC: 846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23
DANN	Benign	0.42
PhyloP100		-0.87
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: rs880900; hg19: chr6-167139479;