rs7543221

Positions:

• chr1-100462868-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The ENST00000336454.5(CDC14A):​c.825C>T​(p.Ala275=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,613,466 control chromosomes in the GnomAD database, including 1,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (834 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (704 hom.)
• Consequence: CDC14A ENST00000336454.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.645

Genes affected

CDC14A (HGNC:1718): (cell division cycle 14A) The protein encoded by this gene is a member of the dual specificity protein tyrosine phosphatase family. It is highly similar to Saccharomyces cerevisiae Cdc14, a protein tyrosine phosphatase involved in the exit of cell mitosis and initiation of DNA replication, suggesting a role in cell cycle control. This protein has been shown to interact with, and dephosphorylate tumor suppressor protein p53, and is thought to regulate the function of p53. Alternative splicing of this gene results in several transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 1-100462868-C-T is Benign according to our data. Variant chr1-100462868-C-T is described in ClinVar as [Benign]. Clinvar id is 517533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.645 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC14A	NM_003672.4	c.825C>T	p.Ala275=	synonymous_variant	9/16	ENST00000336454.5	NP_003663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC14A	ENST00000336454.5	c.825C>T	p.Ala275=	synonymous_variant	9/16	1	NM_003672.4	ENSP00000336739	A1
	ENST00000432210.1	n.123G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.0563 AC: 8548 AN: 151920 Hom.: 829 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0194

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000834

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000662

Gnomad OTH AF: 0.0393

GnomAD3 exomes AF: 0.0154 AC: 3861 AN: 250904 Hom.: 360 AF XY: 0.0111 AC XY: 1504 AN XY: 135634

Gnomad AFR exome AF: 0.204

Gnomad AMR exome AF: 0.00940

Gnomad ASJ exome AF: 0.00695

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000490

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000829

Gnomad OTH exome AF: 0.00768

GnomAD4 exome AF: 0.00598 AC: 8742 AN: 1461428 Hom.: 704 Cov.: 30 AF XY: 0.00521 AC XY: 3790 AN XY: 727032

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.0109

Gnomad4 ASJ exome AF: 0.00524

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000638

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 0.000451

Gnomad4 OTH exome AF: 0.0132

GnomAD4 genome AF: 0.0564 AC: 8579 AN: 152038 Hom.: 834 Cov.: 32 AF XY: 0.0545 AC XY: 4052 AN XY: 74302

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.0191

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000626

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000662

Gnomad4 OTH AF: 0.0389

Alfa AF: 0.0118 Hom.: 279

Bravo AF: 0.0633

Asia WGS AF: 0.0110 AC: 38 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.00124

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 23, 2017	p.Ala275Ala in exon 9 of CDC14A: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 19.94% (2053/10294) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs7543221). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 05, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	4.2
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs7543221; hg19: chr1-100928424;