1-100499154-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003672.4(CDC14A):c.1647C>T(p.Ser549Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,614,092 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 42 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 36 hom. )

Consequence

CDC14A
NM_003672.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.53

Publications

2 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 1-100499154-C-T is Benign according to our data. Variant chr1-100499154-C-T is described in ClinVar as Benign. ClinVar VariationId is 517535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.53 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0115 (1750/152228) while in subpopulation AFR AF = 0.04 (1659/41516). AF 95% confidence interval is 0.0384. There are 42 homozygotes in GnomAd4. There are 864 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC14A	NM_003672.4 link	c.1647C>T	p.Ser549Ser	synonymous_variant	Exon 15 of 16	ENST00000336454.5	NP_003663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC14A	ENST00000336454.5 link	c.1647C>T	p.Ser549Ser	synonymous_variant	Exon 15 of 16	1	NM_003672.4	ENSP00000336739.3

Frequencies

GnomAD3 genomes

AF:

0.0115

AC:

1745

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0400

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00860

GnomAD2 exomes

AF:

0.00290

AC:

728

AN:

250970

AF XY:

0.00214

show subpopulations

Gnomad AFR exome

AF:

0.0397

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000970

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00113

AC:

1652

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

736

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.0394

AC:

1318

AN:

33478

American (AMR)

AF:

0.00195

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.000128

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00329

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000432

AC:

AN:

1112000

Other (OTH)

AF:

0.00278

AC:

168

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

107

214

321

428

535

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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:

0.0115

AC:

1750

AN:

152228

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

864

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0400

AC:

1659

AN:

41516

American (AMR)

AF:

0.00418

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68008

Other (OTH)

AF:

0.00851

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

170

254

339

424

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00422

Hom.:

Bravo

AF:

0.0124

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

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.Ser549Ser in exon 15 of CDC14A: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 4.10% (424/10342) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs35385659). -

Dec 22, 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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 13, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

1.8

(source)

DANN

Benign

0.58

PhyloP100

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(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