Variant 6-166423304-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_021135.6(RPS6KA2):c.1695C>T(p.Asn565=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00374 in 1,613,970 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 19 hom. )

Consequence

RPS6KA2
NM_021135.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.735

Variant links:

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]

RPS6KA2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 6-166423304-G-A is Benign according to our data. Variant chr6-166423304-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 770932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.735 with no splicing effect.

BS2

High AC in GnomAd4 at 458 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA2	NM_021135.6 linkuse as main transcript	c.1695C>T	p.Asn565=	synonymous_variant	17/21	ENST00000265678.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA2	ENST00000265678.9 linkuse as main transcript	c.1695C>T	p.Asn565=	synonymous_variant	17/21	1	NM_021135.6	P1	Q15349-1

Frequencies

GnomAD3 genomes

AF:

0.00301

AC:

458

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000699

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00451

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00469

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00300

AC:

754

AN:

251154

Hom.:

AF XY:

0.00309

AC XY:

419

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00391

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00147

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00432

Gnomad OTH exome

AF:

0.00685

GnomAD4 exome

AF:

0.00381

AC:

5572

AN:

1461628

Hom.:

Cov.:

AF XY:

0.00383

AC XY:

2783

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00369

Gnomad4 ASJ exome

AF:

0.00222

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00189

Gnomad4 FIN exome

AF:

0.000244

Gnomad4 NFE exome

AF:

0.00439

Gnomad4 OTH exome

AF:

0.00366

GnomAD4 genome

AF:

0.00301

AC:

458

AN:

152342

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

217

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000697

Gnomad4 AMR

AF:

0.00451

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00469

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00393

Hom.:

Bravo

AF:

0.00322

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00431

EpiControl

AF:

0.00545

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	RPS6KA2: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jul 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

3.9

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over