6-166774975-G-T

Variant names:

• chr6-166774975-G-T
• rs2072640
• NM_001318936.2:c.124-4062C>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.124-4062C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0953 in 151,936 control chromosomes in the GnomAD database, including 1,242 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 0.095 (1242 hom., cov: 32)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.450
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	NM_001318936.2		c.124-4062C>A		intron	N/A	NP_001305865.2
	RPS6KA2	NM_001006932.3		c.123+83225C>A		intron	N/A	NP_001006933.3
	RPS6KA2	NM_001318937.2		c.37+87133C>A		intron	N/A	NP_001305866.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA2	ENST00000510118.5	TSL:2	c.124-4062C>A		intron	N/A	ENSP00000422435.1
	RPS6KA2	ENST00000503859.5	TSL:2	c.123+83225C>A		intron	N/A	ENSP00000427015.1
	RPS6KA2	ENST00000506565.1	TSL:4	c.124-4062C>A		intron	N/A	ENSP00000425148.1

Frequencies

GnomAD3 genomes AF: 0.0954 AC: 14481 AN: 151818 Hom.: 1241 Cov.: 32

Gnomad AFR AF: 0.0424

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.0723

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0803

Gnomad OTH AF: 0.0986

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

GnomAD4 genome AF: 0.0953 AC: 14476 AN: 151936 Hom.: 1242 Cov.: 32 AF XY: 0.0993 AC XY: 7373 AN XY: 74262

African (AFR) AF: 0.0424 AC: 1754 AN: 41390

American (AMR) AF: 0.111 AC: 1699 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 727 AN: 3470

East Asian (EAS) AF: 0.479 AC: 2464 AN: 5148

South Asian (SAS) AF: 0.259 AC: 1246 AN: 4816

European-Finnish (FIN) AF: 0.0723 AC: 765 AN: 10578

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0803 AC: 5457 AN: 67964

Other (OTH) AF: 0.0990 AC: 209 AN: 2112

Alfa AF: 0.0945 Hom.: 1782

Bravo AF: 0.0980

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.65
DANN	Benign	0.44
PhyloP100		-0.45
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: rs2072640; hg19: chr6-167188463;