rs2864

Positions:

• chr5-138187741-T-C

Variant summary

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

The ENST00000394886.7(CDC23):​c.*1237A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 239,498 control chromosomes in the GnomAD database, including 13,856 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 0.30 (7542 hom., cov: 32)
  • Exomes 𝑓: 0.37 (6314 hom.)
• Consequence: CDC23 ENST00000394886.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300

Genes affected

CDC23 (HGNC:1724): (cell division cycle 23) The protein encoded by this gene shares strong similarity with Saccharomyces cerevisiae Cdc23, a protein essential for cell cycle progression through the G2/M transition. This protein is a component of anaphase-promoting complex (APC), which is composed of eight protein subunits and highly conserved in eukaryotic cells. APC catalyzes the formation of cyclin B-ubiquitin conjugate that is responsible for the ubiquitin-mediated proteolysis of B-type cyclins. This protein and 3 other members of the APC complex contain the TPR (tetratricopeptide repeat), a protein domain important for protein-protein interaction. [provided by RefSeq, Jul 2008]

KIF20A (HGNC:9787): (kinesin family member 20A) Enables protein kinase binding activity. Involved in microtubule bundle formation; midbody abscission; and regulation of cytokinesis. Located in several cellular components, including cleavage furrow; intercellular bridge; and midbody. Implicated in restrictive cardiomyopathy. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC23	NM_004661.4	c.*1237A>G		3_prime_UTR_variant	16/16	ENST00000394886.7	NP_004652.2
KIF20A	NM_005733.3			downstream_gene_variant		ENST00000394894.8	NP_005724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC23	ENST00000394886.7	c.*1237A>G		3_prime_UTR_variant	16/16	1	NM_004661.4	ENSP00000378350	P1
KIF20A	ENST00000394894.8			downstream_gene_variant		1	NM_005733.3	ENSP00000378356	P1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44867 AN: 151980 Hom.: 7530 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.372 AC: 32508 AN: 87398 Hom.: 6314 Cov.: 0 AF XY: 0.383 AC XY: 17643 AN XY: 46106

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.392

Gnomad4 ASJ exome AF: 0.293

Gnomad4 EAS exome AF: 0.411

Gnomad4 SAS exome AF: 0.454

Gnomad4 FIN exome AF: 0.336

Gnomad4 NFE exome AF: 0.364

Gnomad4 OTH exome AF: 0.342

GnomAD4 genome AF: 0.295 AC: 44899 AN: 152100 Hom.: 7542 Cov.: 32 AF XY: 0.299 AC XY: 22249 AN XY: 74364

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.286

Alfa AF: 0.342 Hom.: 12124

Bravo AF: 0.289

Asia WGS AF: 0.364 AC: 1264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97

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: rs2864; hg19: chr5-137523430;