1-100353717-T-C

Position:

• chr1-100353717-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003672.4(CDC14A):​c.50-45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,009,098 control chromosomes in the GnomAD database, including 18,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3060 hom., cov: 32)
  • Exomes 𝑓: 0.18 (15202 hom.)
• Consequence: CDC14A NM_003672.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.796

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-100353717-T-C is Benign according to our data. Variant chr1-100353717-T-C is described in ClinVar as [Benign]. Clinvar id is 682965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC14A	NM_003672.4	c.50-45T>C		intron_variant		ENST00000336454.5	NP_003663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC14A	ENST00000336454.5	c.50-45T>C		intron_variant		1	NM_003672.4	ENSP00000336739.3

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29852 AN: 152074 Hom.: 3050 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.189

GnomAD3 exomes AF: 0.174 AC: 31886 AN: 183530 Hom.: 2969 AF XY: 0.173 AC XY: 16878 AN XY: 97488

Gnomad AFR exome AF: 0.218

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.225

Gnomad EAS exome AF: 0.127

Gnomad SAS exome AF: 0.104

Gnomad FIN exome AF: 0.245

Gnomad NFE exome AF: 0.195

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.182 AC: 156130 AN: 856906 Hom.: 15202 Cov.: 11 AF XY: 0.179 AC XY: 79933 AN XY: 445428

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.221

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.196 AC: 29878 AN: 152192 Hom.: 3060 Cov.: 32 AF XY: 0.196 AC XY: 14595 AN XY: 74406

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.193

Alfa AF: 0.192 Hom.: 2958

Bravo AF: 0.194

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.0
DANN	Benign	0.79

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: rs2297170; hg19: chr1-100819273; COSMIC: COSV60560153;