rs7770200

Variant names:

• chr6-166737975-A-G
• rs7770200
• NM_001318936.2:c.174+32888T>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+32888T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,148 control chromosomes in the GnomAD database, including 3,992 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 0.21 (3992 hom., cov: 33)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 6 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_001318936.2	c.174+32888T>C		intron_variant	Intron 3 of 22		NP_001305865.2
RPS6KA2	NM_001006932.3	c.123+120225T>C		intron_variant	Intron 2 of 21		NP_001006933.3
RPS6KA2	NM_001318937.2	c.37+124133T>C		intron_variant	Intron 1 of 18		NP_001305866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000510118.5	c.174+32888T>C		intron_variant	Intron 3 of 22	2		ENSP00000422435.1
RPS6KA2	ENST00000503859.5	c.123+120225T>C		intron_variant	Intron 2 of 21	2		ENSP00000427015.1
RPS6KA2	ENST00000506565.1	c.174+32888T>C		intron_variant	Intron 4 of 7	4		ENSP00000425148.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31573 AN: 152030 Hom.: 3969 Cov.: 33

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.208 AC: 31644 AN: 152148 Hom.: 3992 Cov.: 33 AF XY: 0.208 AC XY: 15486 AN XY: 74376

African (AFR) AF: 0.357 AC: 14783 AN: 41460

American (AMR) AF: 0.153 AC: 2341 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 559 AN: 3470

East Asian (EAS) AF: 0.232 AC: 1201 AN: 5176

South Asian (SAS) AF: 0.121 AC: 586 AN: 4828

European-Finnish (FIN) AF: 0.162 AC: 1719 AN: 10582

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9722 AN: 68020

Other (OTH) AF: 0.210 AC: 443 AN: 2112

Alfa AF: 0.165 Hom.: 7468

Bravo AF: 0.215

Asia WGS AF: 0.213 AC: 742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.098
DANN	Benign	0.39
PhyloP100		-1.4
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: rs7770200; hg19: chr6-167151463;