rs1052874

Variant names:

• chr8-27810202-C-G
• rs1052874
• NM_018492.4:c.*103G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018492.4(PBK):​c.*103G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 776,534 control chromosomes in the GnomAD database, including 8,800 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 0.16 (2393 hom., cov: 32)
  • Exomes 𝑓: 0.13 (6407 hom.)
• Consequence: PBK NM_018492.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.478
• Publications: 14 publications found

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: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 Gene-Disease associations (from GenCC):

• Roberts-SC phocomelia syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• Roberts syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018492.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBK	NM_018492.4	MANE Select	c.*103G>C		3_prime_UTR	Exon 8 of 8	NP_060962.2
	PBK	NM_001278945.2		c.*103G>C		3_prime_UTR	Exon 8 of 8	NP_001265874.1
	PBK	NM_001363040.2		c.*103G>C		3_prime_UTR	Exon 8 of 8	NP_001349969.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBK	ENST00000301905.9	TSL:1 MANE Select	c.*103G>C		3_prime_UTR	Exon 8 of 8	ENSP00000301905.4
	ESCO2	ENST00000522378.5	TSL:1	n.*862-1103C>G		intron	N/A	ENSP00000428928.1
	PBK	ENST00000522944.5	TSL:2	c.*103G>C		splice_region	Exon 8 of 8	ENSP00000428489.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23934 AN: 151988 Hom.: 2392 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.0859

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0983

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.126 AC: 78950 AN: 624428 Hom.: 6407 Cov.: 8 AF XY: 0.129 AC XY: 43143 AN XY: 334882

African (AFR) AF: 0.248 AC: 3713 AN: 14964

American (AMR) AF: 0.0981 AC: 2407 AN: 24534

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 3563 AN: 18768

East Asian (EAS) AF: 0.334 AC: 11116 AN: 33322

South Asian (SAS) AF: 0.192 AC: 11056 AN: 57702

European-Finnish (FIN) AF: 0.0891 AC: 4131 AN: 46354

Middle Eastern (MID) AF: 0.176 AC: 709 AN: 4036

European-Non Finnish (NFE) AF: 0.0957 AC: 37572 AN: 392442

Other (OTH) AF: 0.145 AC: 4683 AN: 32306

GnomAD4 genome AF: 0.157 AC: 23942 AN: 152106 Hom.: 2393 Cov.: 32 AF XY: 0.157 AC XY: 11686 AN XY: 74372

African (AFR) AF: 0.253 AC: 10495 AN: 41464

American (AMR) AF: 0.128 AC: 1954 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 649 AN: 3470

East Asian (EAS) AF: 0.367 AC: 1896 AN: 5170

South Asian (SAS) AF: 0.194 AC: 937 AN: 4820

European-Finnish (FIN) AF: 0.0859 AC: 910 AN: 10590

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.0983 AC: 6683 AN: 67988

Other (OTH) AF: 0.167 AC: 351 AN: 2108

Alfa AF: 0.121 Hom.: 186

Bravo AF: 0.164

Asia WGS AF: 0.261 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.4
DANN	Benign	0.71
PhyloP100		0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1052874; hg19: chr8-27667719; COSMIC: COSV57272767; COSMIC: COSV57272767;