chr6-166772186-A-T

Position:

• chr6-166772186-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001318936.2(RPS6KA2):​c.124-1273T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: RPS6KA2 NM_001318936.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA2	NM_001006932.3	c.123+86014T>A		intron_variant
RPS6KA2	NM_001318936.2	c.124-1273T>A		intron_variant
RPS6KA2	NM_001318937.2	c.37+89922T>A		intron_variant
RPS6KA2	XM_047419235.1	c.-169+86014T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA2	ENST00000503859.5	c.123+86014T>A		intron_variant		2
RPS6KA2	ENST00000506565.1	c.124-1273T>A		intron_variant		4
RPS6KA2	ENST00000510118.5	c.124-1273T>A		intron_variant		2
RPS6KA2	ENST00000512860.5	c.-169+134172T>A		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
DANN	Benign	0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6456123; hg19: chr6-167185674;