rs2304854

Variant names:

• chr17-80099763-A-G
• rs2304854
• NM_017950.4:c.3417A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-80099763-A-G
• chr17-80099763-A-C
• chr17-80099763-A-T

Variant summary

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

The NM_017950.4(CCDC40):​c.3417A>G​(p.Pro1139Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 1,612,434 control chromosomes in the GnomAD database, including 171,762 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (18977 hom., cov: 31)
  • Exomes 𝑓: 0.45 (152785 hom.)
• Consequence: CCDC40 NM_017950.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -1.08
• Publications: 25 publications found

Genes affected

CCDC40 (HGNC:26090): (coiled-coil domain 40 molecular ruler complex subunit) This gene encodes a protein that is necessary for motile cilia function. It functions in correct left-right axis formation by regulating the assembly of the inner dynein arm and the dynein regulatory complexes, which control ciliary beat. Mutations in this gene cause ciliary dyskinesia type 15, a disorder due to defects in cilia motility. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

CCDC40 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 15

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Ambry Genetics, Laboratory for Molecular Medicine
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autoimmune disease

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-80099763-A-G is Benign according to our data. Variant chr17-80099763-A-G is described in ClinVar as Benign. ClinVar VariationId is 178712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017950.4. 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
	CCDC40	NM_017950.4	MANE Select	c.3417A>G	p.Pro1139Pro	synonymous	Exon 20 of 20	NP_060420.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC40	ENST00000397545.9	TSL:5 MANE Select	c.3417A>G	p.Pro1139Pro	synonymous	Exon 20 of 20	ENSP00000380679.4	Q4G0X9-1
	CCDC40	ENST00000574799.5	TSL:1	n.2954A>G		non_coding_transcript_exon	Exon 16 of 16
	CCDC40	ENST00000897784.1		c.3609A>G	p.Pro1203Pro	synonymous	Exon 21 of 21	ENSP00000567843.1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74666 AN: 151786 Hom.: 18954 Cov.: 31

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.466

GnomAD2 exomes AF: 0.451 AC: 111378 AN: 247100 AF XY: 0.461

Gnomad AFR exome AF: 0.610

Gnomad AMR exome AF: 0.237

Gnomad ASJ exome AF: 0.499

Gnomad EAS exome AF: 0.410

Gnomad FIN exome AF: 0.536

Gnomad NFE exome AF: 0.460

Gnomad OTH exome AF: 0.475

GnomAD4 exome AF: 0.454 AC: 662967 AN: 1460530 Hom.: 152785 Cov.: 50 AF XY: 0.457 AC XY: 331983 AN XY: 726564

African (AFR) AF: 0.615 AC: 20587 AN: 33468

American (AMR) AF: 0.253 AC: 11284 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 13049 AN: 26112

East Asian (EAS) AF: 0.454 AC: 18015 AN: 39684

South Asian (SAS) AF: 0.513 AC: 44213 AN: 86238

European-Finnish (FIN) AF: 0.542 AC: 28462 AN: 52554

Middle Eastern (MID) AF: 0.545 AC: 3141 AN: 5764

European-Non Finnish (NFE) AF: 0.446 AC: 495963 AN: 1111674

Other (OTH) AF: 0.468 AC: 28253 AN: 60364

GnomAD4 genome AF: 0.492 AC: 74734 AN: 151904 Hom.: 18977 Cov.: 31 AF XY: 0.491 AC XY: 36484 AN XY: 74242

African (AFR) AF: 0.605 AC: 25056 AN: 41424

American (AMR) AF: 0.331 AC: 5064 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1684 AN: 3468

East Asian (EAS) AF: 0.425 AC: 2179 AN: 5130

South Asian (SAS) AF: 0.511 AC: 2468 AN: 4826

European-Finnish (FIN) AF: 0.542 AC: 5731 AN: 10580

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.457 AC: 30990 AN: 67878

Other (OTH) AF: 0.469 AC: 989 AN: 2110

Alfa AF: 0.460 Hom.: 42299

Bravo AF: 0.479

EpiCase AF: 0.454

EpiControl AF: 0.453

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Primary ciliary dyskinesia (3)
-	-	3	Primary ciliary dyskinesia 15 (3)
-	-	2	not provided (2)
-	-	1	Glycogen storage disease, type II (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.060
DANN	Benign	0.34
PhyloP100		-1.1
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: rs2304854; hg19: chr17-78073562; COSMIC: COSV56409368; COSMIC: COSV56409368;