1-100352622-G-C

Position:

• chr1-100352622-G-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_003672.4(CDC14A):​c.-333G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,167,510 control chromosomes in the GnomAD database, including 83,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9799 hom., cov: 32)
  • Exomes 𝑓: 0.38 (73458 hom.)
• Consequence: CDC14A NM_003672.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.02

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 1-100352622-G-C is Benign according to our data. Variant chr1-100352622-G-C is described in ClinVar as [Benign]. Clinvar id is 1234793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC14A	NM_003672.4	c.-333G>C		5_prime_UTR_variant	1/16	ENST00000336454.5	NP_003663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC14A	ENST00000336454.5	c.-333G>C		5_prime_UTR_variant	1/16	1	NM_003672.4	ENSP00000336739.3

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53137 AN: 152022 Hom.: 9791 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.378 AC: 383412 AN: 1015372 Hom.: 73458 Cov.: 31 AF XY: 0.379 AC XY: 182455 AN XY: 480900

Gnomad4 AFR exome AF: 0.205

Gnomad4 AMR exome AF: 0.426

Gnomad4 ASJ exome AF: 0.364

Gnomad4 EAS exome AF: 0.486

Gnomad4 SAS exome AF: 0.456

Gnomad4 FIN exome AF: 0.393

Gnomad4 NFE exome AF: 0.376

Gnomad4 OTH exome AF: 0.377

GnomAD4 genome AF: 0.349 AC: 53159 AN: 152138 Hom.: 9799 Cov.: 32 AF XY: 0.352 AC XY: 26188 AN XY: 74372

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.344

Alfa AF: 0.372 Hom.: 1430

Bravo AF: 0.346

Asia WGS AF: 0.422 AC: 1464 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	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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: rs529224; hg19: chr1-100818178;