Variant rs2294092 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_018492.4(PBK):c.822G>C(p.Ala274=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 1,605,480 control chromosomes in the GnomAD database, including 152,074 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 0.43 ( 14498 hom., cov: 32)

Exomes 𝑓: 0.43 ( 137576 hom. )

Consequence

PBK
NM_018492.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.154

Variant links:

Genes affected

PBK (HGNC:18282): (PDZ binding kinase) This gene encodes a serine/threonine protein kinase related to the dual specific mitogen-activated protein kinase kinase (MAPKK) family. Evidence suggests that mitotic phosphorylation is required for its catalytic activity. The encoded protein may be involved in the activation of lymphoid cells and support testicular functions, with a suggested role in the process of spermatogenesis. Overexpression of this gene has been implicated in tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

PBK links:

ESCO2 (HGNC:27230): (establishment of sister chromatid cohesion N-acetyltransferase 2) This gene encodes a protein that may have acetyltransferase activity and may be required for the establishment of sister chromatid cohesion during the S phase of mitosis. Mutations in this gene have been associated with Roberts syndrome. [provided by RefSeq, Jul 2008]

ESCO2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP7

Synonymous conserved (PhyloP=-0.154 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBK	NM_018492.4 linkuse as main transcript	c.822G>C	p.Ala274=	synonymous_variant	8/8	ENST00000301905.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBK	ENST00000301905.9 linkuse as main transcript	c.822G>C	p.Ala274=	synonymous_variant	8/8	1	NM_018492.4	P1	Q96KB5-1
ESCO2	ENST00000522378.5 linkuse as main transcript	c.*862-853C>G		intron_variant, NMD_transcript_variant		1
PBK	ENST00000522944.5 linkuse as main transcript	c.855G>C	p.Ala285=	synonymous_variant	8/8	2			Q96KB5-2
PBK	ENST00000524266.1 linkuse as main transcript	c.*317G>C		3_prime_UTR_variant, NMD_transcript_variant	6/6	5

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

65961

AN:

151786

Hom.:

14501

Cov.:

show subpopulations

Gnomad AFR

AF:

0.421

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.423

Gnomad ASJ

AF:

0.600

Gnomad EAS

AF:

0.384

Gnomad SAS

AF:

0.415

Gnomad FIN

AF:

0.470

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.437

Gnomad OTH

AF:

0.469

GnomAD3 exomes

AF:

0.429

AC:

107490

AN:

250276

Hom.:

23615

AF XY:

0.434

AC XY:

58811

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.418

Gnomad AMR exome

AF:

0.345

Gnomad ASJ exome

AF:

0.591

Gnomad EAS exome

AF:

0.396

Gnomad SAS exome

AF:

0.416

Gnomad FIN exome

AF:

0.471

Gnomad NFE exome

AF:

0.442

Gnomad OTH exome

AF:

0.460

GnomAD4 exome

AF:

0.432

AC:

628575

AN:

1453576

Hom.:

137576

Cov.:

AF XY:

0.434

AC XY:

313892

AN XY:

723616

show subpopulations

Gnomad4 AFR exome

AF:

0.413

Gnomad4 AMR exome

AF:

0.359

Gnomad4 ASJ exome

AF:

0.589

Gnomad4 EAS exome

AF:

0.380

Gnomad4 SAS exome

AF:

0.420

Gnomad4 FIN exome

AF:

0.462

Gnomad4 NFE exome

AF:

0.432

Gnomad4 OTH exome

AF:

0.454

GnomAD4 genome

AF:

0.434

AC:

65988

AN:

151904

Hom.:

14498

Cov.:

AF XY:

0.437

AC XY:

32419

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.421

Gnomad4 AMR

AF:

0.423

Gnomad4 ASJ

AF:

0.600

Gnomad4 EAS

AF:

0.384

Gnomad4 SAS

AF:

0.414

Gnomad4 FIN

AF:

0.470

Gnomad4 NFE

AF:

0.437

Gnomad4 OTH

AF:

0.467

Alfa

AF:

0.415

Hom.:

3964

Bravo

AF:

0.430

Asia WGS

AF:

0.391

AC:

1366

AN:

3478

EpiCase

AF:

0.470

EpiControl

AF:

0.469

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

7.2

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over