rs2864

Variant names:

• chr5-138187741-T-C
• rs2864
• NM_004661.4:c.*1237A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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]

KIF20A Gene-Disease associations (from GenCC):

• familial isolated restrictive cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cardiomyopathy, familial restrictive, 6

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000394886.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC23	NM_004661.4	MANE Select	c.*1237A>G		3_prime_UTR	Exon 16 of 16	NP_004652.2
	KIF20A	NM_005733.3	MANE Select	c.*328T>C		downstream_gene	N/A	NP_005724.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC23	ENST00000394886.7	TSL:1 MANE Select	c.*1237A>G		3_prime_UTR	Exon 16 of 16	ENSP00000378350.2
	KIF20A	ENST00000394894.8	TSL:1 MANE Select	c.*328T>C		downstream_gene	N/A	ENSP00000378356.3
	KIF20A	ENST00000508792.5	TSL:2	c.*328T>C		downstream_gene	N/A	ENSP00000420880.1

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

African (AFR) AF: 0.142 AC: 278 AN: 1956

American (AMR) AF: 0.392 AC: 1572 AN: 4014

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 627 AN: 2140

East Asian (EAS) AF: 0.411 AC: 1661 AN: 4046

South Asian (SAS) AF: 0.454 AC: 6177 AN: 13596

European-Finnish (FIN) AF: 0.336 AC: 1349 AN: 4016

Middle Eastern (MID) AF: 0.304 AC: 90 AN: 296

European-Non Finnish (NFE) AF: 0.364 AC: 19223 AN: 52858

Other (OTH) AF: 0.342 AC: 1531 AN: 4476

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

African (AFR) AF: 0.137 AC: 5684 AN: 41518

American (AMR) AF: 0.373 AC: 5689 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1084 AN: 3468

East Asian (EAS) AF: 0.383 AC: 1984 AN: 5176

South Asian (SAS) AF: 0.420 AC: 2025 AN: 4820

European-Finnish (FIN) AF: 0.330 AC: 3492 AN: 10572

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24112 AN: 67980

Other (OTH) AF: 0.286 AC: 600 AN: 2100

Alfa AF: 0.336 Hom.: 14856

Bravo AF: 0.289

Asia WGS AF: 0.364 AC: 1264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.78
PhyloP100		-0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97
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: rs2864; hg19: chr5-137523430;