Variant 6-166412777-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The ENST00000265678.9(RPS6KA2):c.2187G>C(p.Thr729=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,598,718 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 42 hom., cov: 35)

Exomes 𝑓: 0.0013 ( 38 hom. )

Consequence

RPS6KA2
ENST00000265678.9 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.793

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=-0.51).

BP6

Variant 6-166412777-C-G is Benign according to our data. Variant chr6-166412777-C-G is described in ClinVar as [Benign]. Clinvar id is 781018.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.793 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0112 (1711/152320) while in subpopulation AFR AF= 0.0386 (1605/41580). AF 95% confidence interval is 0.037. There are 42 homozygotes in gnomad4. There are 827 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1711 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA2	NM_021135.6 linkuse as main transcript	c.2187G>C	p.Thr729=	synonymous_variant	21/21	ENST00000265678.9	NP_066958.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA2	ENST00000265678.9 linkuse as main transcript	c.2187G>C	p.Thr729=	synonymous_variant	21/21	1	NM_021135.6	ENSP00000265678	P1	Q15349-1

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

1695

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0383

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00279

AC:

619

AN:

221642

Hom.:

AF XY:

0.00206

AC XY:

246

AN XY:

119684

show subpopulations

Gnomad AFR exome

AF:

0.0375

Gnomad AMR exome

AF:

0.00225

Gnomad ASJ exome

AF:

0.000860

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000148

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000170

Gnomad OTH exome

AF:

0.00203

GnomAD4 exome

AF:

0.00132

AC:

1914

AN:

1446398

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

828

AN XY:

717942

show subpopulations

Gnomad4 AFR exome

AF:

0.0408

Gnomad4 AMR exome

AF:

0.00278

Gnomad4 ASJ exome

AF:

0.000624

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000117

Gnomad4 OTH exome

AF:

0.00391

GnomAD4 genome

AF:

0.0112

AC:

1711

AN:

152320

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

827

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0386

Gnomad4 AMR

AF:

0.00457

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.000767

Hom.:

Bravo

AF:

0.0131

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.26

DANN

Benign

0.63

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