rs10484520

Variant names:

• chr6-166801198-G-A
• rs10484520
• XR_007059865.1:n.184C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007059865.1(LOC124901459):​n.184C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0426 in 152,164 control chromosomes in the GnomAD database, including 545 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 0.043 (545 hom., cov: 33)
• Consequence: LOC124901459 XR_007059865.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 6 publications found

Genes affected

LOC124901459 (HGNC:):

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 = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124901459	XR_007059865.1	n.184C>T		non_coding_transcript_exon_variant	Exon 1 of 2
RPS6KA2	NM_001318936.2	c.124-30285C>T		intron_variant	Intron 2 of 22		NP_001305865.2
RPS6KA2	NM_001006932.3	c.123+57002C>T		intron_variant	Intron 2 of 21		NP_001006933.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000510118.5	c.124-30285C>T		intron_variant	Intron 2 of 22	2		ENSP00000422435.1
RPS6KA2	ENST00000503859.5	c.123+57002C>T		intron_variant	Intron 2 of 21	2		ENSP00000427015.1
RPS6KA2	ENST00000506565.1	c.124-30285C>T		intron_variant	Intron 3 of 7	4		ENSP00000425148.1
RPS6KA2	ENST00000512860.5	c.-169+105160C>T		intron_variant	Intron 1 of 5	4		ENSP00000427605.1

Frequencies

GnomAD3 genomes AF: 0.0426 AC: 6480 AN: 152046 Hom.: 544 Cov.: 33

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0690

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0785

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0201

Gnomad OTH AF: 0.0353

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

GnomAD4 genome AF: 0.0426 AC: 6486 AN: 152164 Hom.: 545 Cov.: 33 AF XY: 0.0483 AC XY: 3594 AN XY: 74412

African (AFR) AF: 0.0124 AC: 515 AN: 41494

American (AMR) AF: 0.0693 AC: 1060 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3468

East Asian (EAS) AF: 0.390 AC: 2019 AN: 5180

South Asian (SAS) AF: 0.117 AC: 563 AN: 4818

European-Finnish (FIN) AF: 0.0785 AC: 831 AN: 10582

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0201 AC: 1366 AN: 68002

Other (OTH) AF: 0.0373 AC: 79 AN: 2116

Alfa AF: 0.0364 Hom.: 44

Bravo AF: 0.0429

Asia WGS AF: 0.267 AC: 926 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.67
PhyloP100		-1.0
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: rs10484520; hg19: chr6-167214686;