1-100462868-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_003672.4(CDC14A):c.825C>T(p.Ala275Ala) 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
NM_003672.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.645

Publications

4 publications found

Variant links:

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]

CDC14A Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic deafness 105
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
autosomal recessive nonsyndromic hearing loss 32
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, PanelApp Australia
hearing impairment and infertile male syndrome
Inheritance: AR Classification: STRONG Submitted by: ClinGen
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
nonsyndromic genetic hearing loss
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

CDC14A links:

ENSG00000228086 (HGNC:):

ENSG00000228086 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
CDC14A	NM_003672.4 link	c.825C>T	p.Ala275Ala	synonymous_variant	Exon 9 of 16	ENST00000336454.5	NP_003663.2	Q9UNH5-1Q59EF4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC14A	ENST00000336454.5 link	c.825C>T	p.Ala275Ala	synonymous_variant	Exon 9 of 16	1	NM_003672.4	ENSP00000336739.3		Q9UNH5-1

Frequencies

GnomAD3 genomes

AF:

0.0563

AC:

8548

AN:

151920

Hom.:

829

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0154

AC:

3861

AN:

250904

AF XY:

0.0111

show subpopulations

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 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.:

AF XY:

0.00521

AC XY:

3790

AN XY:

727032

show subpopulations

African (AFR)

AF:

0.200

AC:

6681

AN:

33450

American (AMR)

AF:

0.0109

AC:

489

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00524

AC:

137

AN:

26126

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39656

South Asian (SAS)

AF:

0.000638

AC:

AN:

86206

European-Finnish (FIN)

AF:

0.0000749

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.0130

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000451

AC:

501

AN:

1111722

Other (OTH)

AF:

0.0132

AC:

799

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

391

782

1172

1563

1954

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

206

412

618

824

1030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0564

AC:

8579

AN:

152038

Hom.:

834

Cov.:

AF XY:

0.0545

AC XY:

4052

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.196

AC:

8129

AN:

41440

American (AMR)

AF:

0.0191

AC:

292

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00519

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000626

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000662

AC:

AN:

67980

Other (OTH)

AF:

0.0389

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

339

679

1018

1358

1697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0230

Hom.:

857

Bravo

AF:

0.0633

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.00124

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Aug 23, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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). -

Oct 05, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

4.2

(source)

DANN

Benign

0.92

PhyloP100

-0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=88/12

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over