rs2338436

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_181426.2(CCDC39):c.1248A>G(p.Glu416Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0581 in 1,612,916 control chromosomes in the GnomAD database, including 7,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 3205 hom., cov: 32)

Exomes 𝑓: 0.050 ( 4307 hom. )

Consequence

CCDC39
NM_181426.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.566

Publications

8 publications found

Variant links:

Genes affected

CCDC39 (HGNC:25244): (coiled-coil domain 39 molecular ruler complex subunit) The protein encoded by this gene is involved in the motility of cilia and flagella. The encoded protein is essential for the assembly of dynein regulatory and inner dynein arm complexes, which regulate ciliary beat. Defects in this gene are a cause of primary ciliary dyskinesia type 14 (CILD14). [provided by RefSeq, Jul 2011]

CCDC39 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 14
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CCDC39 links:

ENSG00000145075 (HGNC:):

ENSG00000145075 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=-0.56).

BP6

Variant 3-180648279-T-C is Benign according to our data. Variant chr3-180648279-T-C is described in ClinVar as Benign. ClinVar VariationId is 162843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.566 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC39	NM_181426.2 link	c.1248A>G	p.Glu416Glu	synonymous_variant	Exon 10 of 20	ENST00000476379.6	NP_852091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC39	ENST00000476379.6 link	c.1248A>G	p.Glu416Glu	synonymous_variant	Exon 10 of 20	2	NM_181426.2	ENSP00000417960.2

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20816

AN:

152058

Hom.:

3197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.381

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.0845

Gnomad ASJ

AF:

0.0354

Gnomad EAS

AF:

0.00250

Gnomad SAS

AF:

0.0767

Gnomad FIN

AF:

0.00715

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0415

Gnomad OTH

AF:

0.118

GnomAD2 exomes

AF:

0.0627

AC:

15603

AN:

248748

AF XY:

0.0602

show subpopulations

Gnomad AFR exome

AF:

0.393

Gnomad AMR exome

AF:

0.0452

Gnomad ASJ exome

AF:

0.0370

Gnomad EAS exome

AF:

0.00189

Gnomad FIN exome

AF:

0.00655

Gnomad NFE exome

AF:

0.0408

Gnomad OTH exome

AF:

0.0632

GnomAD4 exome

AF:

0.0499

AC:

72845

AN:

1460740

Hom.:

4307

Cov.:

AF XY:

0.0500

AC XY:

36308

AN XY:

726636

show subpopulations

African (AFR)

AF:

0.400

AC:

13360

AN:

33386

American (AMR)

AF:

0.0505

AC:

2254

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.0355

AC:

928

AN:

26120

East Asian (EAS)

AF:

0.00106

AC:

AN:

39648

South Asian (SAS)

AF:

0.0795

AC:

6847

AN:

86144

European-Finnish (FIN)

AF:

0.00710

AC:

379

AN:

53376

Middle Eastern (MID)

AF:

0.0950

AC:

546

AN:

5746

European-Non Finnish (NFE)

AF:

0.0401

AC:

44529

AN:

1111328

Other (OTH)

AF:

0.0656

AC:

3960

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

2995

5989

8984

11978

14973

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1830

3660

5490

7320

9150

<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:

0.137

AC:

20844

AN:

152176

Hom.:

3205

Cov.:

AF XY:

0.132

AC XY:

9831

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.381

AC:

15777

AN:

41446

American (AMR)

AF:

0.0843

AC:

1289

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0354

AC:

123

AN:

3472

East Asian (EAS)

AF:

0.00251

AC:

AN:

5184

South Asian (SAS)

AF:

0.0761

AC:

367

AN:

4820

European-Finnish (FIN)

AF:

0.00715

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0414

AC:

2816

AN:

68014

Other (OTH)

AF:

0.116

AC:

245

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

747

1494

2242

2989

3736

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:

0.0802

Hom.:

1903

Bravo

AF:

0.154

Asia WGS

AF:

0.0680

AC:

238

AN:

3478

EpiCase

AF:

0.0488

EpiControl

AF:

0.0506

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Glu416Glu in exon 10 of CCDC39: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 37.7% (1380/3662) of African American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2338436). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia

Benign:2

Jul 08, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 21, 2019

GeneDx

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

- -

Primary ciliary dyskinesia 14

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

2.4

(source)

DANN

Benign

0.66

PhyloP100

0.57

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