rs147028259

Variant names:

• chr3-180619381-T-G
• rs147028259
• NM_181426.2:c.2159-16A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0570
• Publications: 1 publications found

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: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000145075 (HGNC:):

ACMG classification

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 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181426.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC39	NM_181426.2	MANE Select	c.2159-16A>C		intron	N/A	NP_852091.1	Q9UFE4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC39	ENST00000476379.6	TSL:2 MANE Select	c.2159-16A>C		intron	N/A	ENSP00000417960.2	Q9UFE4-1
	CCDC39	ENST00000936067.1		c.2066-16A>C		intron	N/A	ENSP00000606126.1
	CCDC39	ENST00000651046.1		c.1967-16A>C		intron	N/A	ENSP00000499175.1	A0A494C1Q3

Frequencies

GnomAD3 genomes AF: 0.00831 AC: 1264 AN: 152118 Hom.: 11 Cov.: 32

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

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.: 87 Cov.: 14 AF XY: 0.0107 AC XY: 5913 AN XY: 552804

African (AFR) AF: 0.00201 AC: 49 AN: 24324

American (AMR) AF: 0.00822 AC: 238 AN: 28964

Ashkenazi Jewish (ASJ) AF: 0.00198 AC: 45 AN: 22776

East Asian (EAS) AF: 0.00 AC: 0 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: 17 AN: 4654

European-Non Finnish (NFE) AF: 0.0128 AC: 10471 AN: 816416

Other (OTH) AF: 0.0105 AC: 499 AN: 47710

GnomAD4 genome AF: 0.00830 AC: 1264 AN: 152236 Hom.: 11 Cov.: 32 AF XY: 0.00758 AC XY: 564 AN XY: 74436

African (AFR) AF: 0.00229 AC: 95 AN: 41562

American (AMR) AF: 0.00694 AC: 106 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4830

European-Finnish (FIN) AF: 0.00858 AC: 91 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0132 AC: 899 AN: 67994

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.00961 Hom.: 4

Bravo AF: 0.00780

Asia WGS AF: 0.000867 AC: 3 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Primary ciliary dyskinesia 14 (2)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.2
DANN	Benign	0.68
PhyloP100		-0.057
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs147028259; hg19: chr3-180337169;