rs147028259

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_181426.2(CCDC39):c.2159-16A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,247,156 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0083 ( 11 hom., cov: 32)

Exomes 𝑓: 0.011 ( 87 hom. )

Consequence

CCDC39
NM_181426.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0570

Publications

1 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 3-180619381-T-G is Benign according to our data. Variant chr3-180619381-T-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0083 (1264/152236) while in subpopulation NFE AF = 0.0132 (899/67994). AF 95% confidence interval is 0.0125. There are 11 homozygotes in GnomAd4. There are 564 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 11 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC39	NM_181426.2 link	c.2159-16A>C		intron_variant	Intron 15 of 19	ENST00000476379.6	NP_852091.1	Q9UFE4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC39	ENST00000476379.6 link	c.2159-16A>C		intron_variant	Intron 15 of 19	2	NM_181426.2	ENSP00000417960.2		Q9UFE4-1

Frequencies

GnomAD3 genomes

AF:

0.00831

AC:

1264

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00229

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.00695

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00858

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0132

Gnomad OTH

AF:

0.00813

GnomAD2 exomes

AF:

0.00875

AC:

1190

AN:

136006

AF XY:

0.00831

show subpopulations

Gnomad AFR exome

AF:

0.00203

Gnomad AMR exome

AF:

0.00922

Gnomad ASJ exome

AF:

0.00216

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00930

Gnomad NFE exome

AF:

0.0135

Gnomad OTH exome

AF:

0.00954

GnomAD4 exome

AF:

0.0110

AC:

12014

AN:

1094920

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

5913

AN XY:

552804

show subpopulations

African (AFR)

AF:

0.00201

AC:

AN:

24324

American (AMR)

AF:

0.00822

AC:

238

AN:

28964

Ashkenazi Jewish (ASJ)

AF:

0.00198

AC:

AN:

22776

East Asian (EAS)

AF:

0.00

AC:

AN:

34106

South Asian (SAS)

AF:

0.00306

AC:

207

AN:

67672

European-Finnish (FIN)

AF:

0.0101

AC:

488

AN:

48298

Middle Eastern (MID)

AF:

0.00365

AC:

AN:

4654

European-Non Finnish (NFE)

AF:

0.0128

AC:

10471

AN:

816416

Other (OTH)

AF:

0.0105

AC:

499

AN:

47710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

576

1151

1727

2302

2878

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

362

724

1086

1448

1810

<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:

0.00830

AC:

1264

AN:

152236

Hom.:

Cov.:

AF XY:

0.00758

AC XY:

564

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.00229

AC:

AN:

41562

American (AMR)

AF:

0.00694

AC:

106

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00269

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00858

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0132

AC:

899

AN:

67994

Other (OTH)

AF:

0.00805

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

134

201

268

335

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:

0.00961

Hom.:

Bravo

AF:

0.00780

Asia WGS

AF:

0.000867

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary ciliary dyskinesia

Benign:1

Jan 25, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Primary ciliary dyskinesia 14

Benign:1

Jan 17, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Likely 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

-0.83

CADD

Benign

5.2

(source)

DANN

Benign

0.68

PhyloP100

-0.057

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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