17-47154771-T-C

Position:

• chr17-47154771-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001256.6(CDC27):​c.858A>G​(p.Pro286Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00339 in 1,586,894 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (13 hom.)
• Consequence: CDC27 NM_001256.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.09

Genes affected

CDC27 (HGNC:1728): (cell division cycle 27) The protein encoded by this gene shares strong similarity with Saccharomyces cerevisiae protein Cdc27, and the gene product of Schizosaccharomyces pombe nuc 2. This protein is a component of the anaphase-promoting complex (APC), which is composed of eight protein subunits and is highly conserved in eukaryotic cells. This complex catalyzes the formation of cyclin B-ubiquitin conjugate, which is responsible for the ubiquitin-mediated proteolysis of B-type cyclins. The protein encoded by this gene and three other members of the APC complex contain tetratricopeptide (TPR) repeats, which are important for protein-protein interactions. This protein was shown to interact with mitotic checkpoint proteins including Mad2, p55CDC and BUBR1, and it may thus be involved in controlling the timing of mitosis. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 2, 22 and Y. [provided by RefSeq, May 2014]

CDC27 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 17-47154771-T-C is Benign according to our data. Variant chr17-47154771-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 782550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.09 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00343 (4927/1434666) while in subpopulation MID AF= 0.0224 (126/5616). AF 95% confidence interval is 0.0193. There are 13 homozygotes in gnomad4_exome. There are 2467 alleles in male gnomad4_exome subpopulation. Median coverage is 24. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 449 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC27	NM_001256.6	c.858A>G	p.Pro286Pro	synonymous_variant	8/19	ENST00000066544.8	NP_001247.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC27	ENST00000066544.8	c.858A>G	p.Pro286Pro	synonymous_variant	8/19	1	NM_001256.6	ENSP00000066544.3

Frequencies

GnomAD3 genomes AF: 0.00296 AC: 450 AN: 152110 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000821

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00401

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00315 AC: 778 AN: 246804 Hom.: 5 AF XY: 0.00336 AC XY: 448 AN XY: 133430

Gnomad AFR exome AF: 0.000885

Gnomad AMR exome AF: 0.00290

Gnomad ASJ exome AF: 0.0132

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00120

Gnomad FIN exome AF: 0.00107

Gnomad NFE exome AF: 0.00398

Gnomad OTH exome AF: 0.00530

GnomAD4 exome AF: 0.00343 AC: 4927 AN: 1434666 Hom.: 13 Cov.: 24 AF XY: 0.00345 AC XY: 2467 AN XY: 715026

Gnomad4 AFR exome AF: 0.00115

Gnomad4 AMR exome AF: 0.00313

Gnomad4 ASJ exome AF: 0.0130

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00105

Gnomad4 FIN exome AF: 0.000994

Gnomad4 NFE exome AF: 0.00359

Gnomad4 OTH exome AF: 0.00407

GnomAD4 genome AF: 0.00295 AC: 449 AN: 152228 Hom.: 2 Cov.: 32 AF XY: 0.00279 AC XY: 208 AN XY: 74434

Gnomad4 AFR AF: 0.000819

Gnomad4 AMR AF: 0.00386

Gnomad4 ASJ AF: 0.0133

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.000660

Gnomad4 NFE AF: 0.00401

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00372 Hom.: 0

Bravo AF: 0.00327

Asia WGS AF: 0.000289 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 01, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	CDC27: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

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: rs61749925; hg19: chr17-45232137; COSMIC: COSV50414383; COSMIC: COSV50414383;