rs7745781

Variant names:

• chr6-166833328-A-G
• rs7745781
• NM_001318936.2:c.123+24872T>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.123+24872T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,282 control chromosomes in the GnomAD database, including 1,499 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 0.13 (1499 hom., cov: 33)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_001318936.2	c.123+24872T>C		intron_variant	Intron 2 of 22		NP_001305865.2
RPS6KA2	NM_001006932.3	c.123+24872T>C		intron_variant	Intron 2 of 21		NP_001006933.3
RPS6KA2	NM_001318937.2	c.37+28780T>C		intron_variant	Intron 1 of 18		NP_001305866.1
RPS6KA2	XM_047419235.1	c.-169+24872T>C		intron_variant	Intron 2 of 21		XP_047275191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000510118.5	c.123+24872T>C		intron_variant	Intron 2 of 22	2		ENSP00000422435.1
RPS6KA2	ENST00000503859.5	c.123+24872T>C		intron_variant	Intron 2 of 21	2		ENSP00000427015.1
RPS6KA2	ENST00000506565.1	c.123+24872T>C		intron_variant	Intron 3 of 7	4		ENSP00000425148.1
RPS6KA2	ENST00000512860.5	c.-169+73030T>C		intron_variant	Intron 1 of 5	4		ENSP00000427605.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19706 AN: 152164 Hom.: 1492 Cov.: 33

Gnomad AFR AF: 0.0649

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.0760

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.130 AC: 19736 AN: 152282 Hom.: 1499 Cov.: 33 AF XY: 0.134 AC XY: 9968 AN XY: 74448

African (AFR) AF: 0.0649 AC: 2700 AN: 41574

American (AMR) AF: 0.193 AC: 2950 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0760 AC: 264 AN: 3472

East Asian (EAS) AF: 0.277 AC: 1437 AN: 5182

South Asian (SAS) AF: 0.194 AC: 937 AN: 4826

European-Finnish (FIN) AF: 0.153 AC: 1618 AN: 10588

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9495 AN: 68016

Other (OTH) AF: 0.122 AC: 259 AN: 2116

Alfa AF: 0.131 Hom.: 521

Bravo AF: 0.127

Asia WGS AF: 0.197 AC: 684 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.85
DANN	Benign	0.46
PhyloP100		-0.39
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: rs7745781; hg19: chr6-167246816;