rs2338436

Variant names:

• chr3-180648279-T-C
• rs2338436
• NM_181426.2:c.1248A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-180648279-T-C
• chr3-180648279-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.566
• Publications: 8 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 -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.

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.1248A>G	p.Glu416Glu	synonymous	Exon 10 of 20	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.1248A>G	p.Glu416Glu	synonymous	Exon 10 of 20	ENSP00000417960.2	Q9UFE4-1
	CCDC39	ENST00000936067.1		c.1155A>G	p.Glu385Glu	synonymous	Exon 9 of 19	ENSP00000606126.1
	CCDC39	ENST00000651046.1		c.1056A>G	p.Glu352Glu	synonymous	Exon 9 of 19	ENSP00000499175.1	A0A494C1Q3

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20816 AN: 152058 Hom.: 3197 Cov.: 32

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

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.: 31 AF XY: 0.0500 AC XY: 36308 AN XY: 726636

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: 42 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

GnomAD4 genome AF: 0.137 AC: 20844 AN: 152176 Hom.: 3205 Cov.: 32 AF XY: 0.132 AC XY: 9831 AN XY: 74420

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: 13 AN: 5184

South Asian (SAS) AF: 0.0761 AC: 367 AN: 4820

European-Finnish (FIN) AF: 0.00715 AC: 76 AN: 10624

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0414 AC: 2816 AN: 68014

Other (OTH) AF: 0.116 AC: 245 AN: 2114

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	2.4
DANN	Benign	0.66
PhyloP100		0.57
Mutation Taster		=100/0	polymorphism (auto)

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: rs2338436; hg19: chr3-180366067; COSMIC: COSV56486370;