6-166751083-C-T

Variant names:

• chr6-166751083-C-T
• rs4710090
• NM_001318936.2:c.174+19780G>A

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+19780G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,088 control chromosomes in the GnomAD database, including 8,176 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 0.31 (8176 hom., cov: 33)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.625
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA2	NM_001318936.2	c.174+19780G>A		intron_variant	Intron 3 of 22		NP_001305865.2
RPS6KA2	NM_001006932.3	c.123+107117G>A		intron_variant	Intron 2 of 21		NP_001006933.3
RPS6KA2	NM_001318937.2	c.37+111025G>A		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+19780G>A		intron_variant	Intron 3 of 22	2		ENSP00000422435.1
RPS6KA2	ENST00000503859.5	c.123+107117G>A		intron_variant	Intron 2 of 21	2		ENSP00000427015.1
RPS6KA2	ENST00000506565.1	c.174+19780G>A		intron_variant	Intron 4 of 7	4		ENSP00000425148.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46983 AN: 151970 Hom.: 8174 Cov.: 33

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.309 AC: 46991 AN: 152088 Hom.: 8176 Cov.: 33 AF XY: 0.311 AC XY: 23135 AN XY: 74318

African (AFR) AF: 0.133 AC: 5526 AN: 41512

American (AMR) AF: 0.385 AC: 5881 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1374 AN: 3470

East Asian (EAS) AF: 0.354 AC: 1825 AN: 5162

South Asian (SAS) AF: 0.340 AC: 1637 AN: 4820

European-Finnish (FIN) AF: 0.404 AC: 4266 AN: 10548

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.371 AC: 25216 AN: 67988

Other (OTH) AF: 0.318 AC: 669 AN: 2106

Alfa AF: 0.333 Hom.: 4463

Bravo AF: 0.303

Asia WGS AF: 0.306 AC: 1064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.56
PhyloP100		0.63
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: rs4710090; hg19: chr6-167164571; COSMIC: COSV72312603;