rs2270694

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003672.4(CDC14A):c.990G>A(p.Ser330Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,562,224 control chromosomes in the GnomAD database, including 12,304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1129 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11175 hom. )

Consequence

CDC14A
NM_003672.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.23

Publications

11 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=-0.72).

BP6

Variant 1-100484304-G-A is Benign according to our data. Variant chr1-100484304-G-A is described in ClinVar as Benign. ClinVar VariationId is 508568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC14A	NM_003672.4 link	c.990G>A	p.Ser330Ser	synonymous_variant	Exon 11 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.990G>A	p.Ser330Ser	synonymous_variant	Exon 11 of 16	1	NM_003672.4	ENSP00000336739.3		Q9UNH5-1

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

16967

AN:

151888

Hom.:

1128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0596

Gnomad AMI

AF:

0.185

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.0618

Gnomad SAS

AF:

0.0936

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.122

GnomAD2 exomes

AF:

0.117

AC:

24079

AN:

205850

AF XY:

0.119

show subpopulations

Gnomad AFR exome

AF:

0.0572

Gnomad AMR exome

AF:

0.0868

Gnomad ASJ exome

AF:

0.214

Gnomad EAS exome

AF:

0.0624

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.130

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.122

AC:

172533

AN:

1410220

Hom.:

11175

Cov.:

AF XY:

0.122

AC XY:

85737

AN XY:

701140

show subpopulations

African (AFR)

AF:

0.0575

AC:

1756

AN:

30528

American (AMR)

AF:

0.0898

AC:

3140

AN:

34984

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

5033

AN:

24294

East Asian (EAS)

AF:

0.0617

AC:

2340

AN:

37904

South Asian (SAS)

AF:

0.0896

AC:

7005

AN:

78196

European-Finnish (FIN)

AF:

0.159

AC:

8279

AN:

52028

Middle Eastern (MID)

AF:

0.130

AC:

726

AN:

5564

European-Non Finnish (NFE)

AF:

0.126

AC:

137205

AN:

1088658

Other (OTH)

AF:

0.121

AC:

7049

AN:

58064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

6006

12011

18017

24022

30028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4944

9888

14832

19776

24720

<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:

0.112

AC:

16972

AN:

152004

Hom.:

1129

Cov.:

AF XY:

0.113

AC XY:

8396

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.0596

AC:

2472

AN:

41492

American (AMR)

AF:

0.117

AC:

1782

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

725

AN:

3472

East Asian (EAS)

AF:

0.0618

AC:

320

AN:

5178

South Asian (SAS)

AF:

0.0937

AC:

452

AN:

4824

European-Finnish (FIN)

AF:

0.169

AC:

1778

AN:

10530

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.132

AC:

8982

AN:

67938

Other (OTH)

AF:

0.120

AC:

252

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

756

1512

2267

3023

3779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

194

388

582

776

970

<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:

0.127

Hom.:

2835

Bravo

AF:

0.106

Asia WGS

AF:

0.0700

AC:

242

AN:

3476

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.Ser330Ser in exon 11 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 21.12% (1071/5072) of Finnish chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs2270694). -

May 09, 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

Feb 03, 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

AlphaMissense

Benign

0.075

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.68

(source)

DANN

Benign

0.84

PhyloP100

-1.2

Mutation Taster

=100/0

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