chr8-27818230-A-G

Position:

• chr8-27818230-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018492.4(PBK):​c.595+2335T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,122 control chromosomes in the GnomAD database, including 13,578 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 0.42 (13578 hom., cov: 33)
• Consequence: PBK NM_018492.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106

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]

ESCO2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PBK	NM_018492.4	c.595+2335T>C		intron_variant		ENST00000301905.9	NP_060962.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PBK	ENST00000301905.9	c.595+2335T>C		intron_variant		1	NM_018492.4	ENSP00000301905	P1
PBK	ENST00000522944.5	c.595+2335T>C		intron_variant		2		ENSP00000428489
PBK	ENST00000524266.1	c.*90+2335T>C		intron_variant, NMD_transcript_variant		5		ENSP00000428438

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63306 AN: 152004 Hom.: 13554 Cov.: 33

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.417 AC: 63387 AN: 152122 Hom.: 13578 Cov.: 33 AF XY: 0.416 AC XY: 30911 AN XY: 74374

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.616

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.407

Alfa AF: 0.438 Hom.: 2506

Bravo AF: 0.427

Asia WGS AF: 0.548 AC: 1901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.6
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs10503818; hg19: chr8-27675747;