rs1982243

Variant names:

• chr17-80095298-G-A
• rs1982243
• NM_017950.4:c.2868G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_017950.4(CCDC40):​c.2868G>A​(p.Lys956Lys) variant causes a synonymous change. The variant allele was found at a frequency of 0.0305 in 1,614,018 control chromosomes in the GnomAD database, including 1,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (114 hom., cov: 34)
  • Exomes 𝑓: 0.030 (1036 hom.)
• Consequence: CCDC40 NM_017950.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 3.88
• Publications: 10 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 17-80095298-G-A is Benign according to our data. Variant chr17-80095298-G-A is described in ClinVar as Benign. ClinVar VariationId is 226492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 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.2868G>A	p.Lys956Lys	synonymous	Exon 18 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.2868G>A	p.Lys956Lys	synonymous	Exon 18 of 20	ENSP00000380679.4	Q4G0X9-1
	CCDC40	ENST00000574799.5	TSL:1	n.2405G>A		non_coding_transcript_exon	Exon 14 of 16
	CCDC40	ENST00000897784.1		c.3060G>A	p.Lys1020Lys	synonymous	Exon 19 of 21	ENSP00000567843.1

Frequencies

GnomAD3 genomes AF: 0.0323 AC: 4911 AN: 152268 Hom.: 115 Cov.: 34

Gnomad AFR AF: 0.0219

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0254

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.0583

Gnomad FIN AF: 0.0417

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0295

Gnomad OTH AF: 0.0411

GnomAD2 exomes AF: 0.0379 AC: 9432 AN: 249086 AF XY: 0.0391

Gnomad AFR exome AF: 0.0228

Gnomad AMR exome AF: 0.0181

Gnomad ASJ exome AF: 0.0313

Gnomad EAS exome AF: 0.126

Gnomad FIN exome AF: 0.0423

Gnomad NFE exome AF: 0.0280

Gnomad OTH exome AF: 0.0380

GnomAD4 exome AF: 0.0304 AC: 44395 AN: 1461632 Hom.: 1036 Cov.: 32 AF XY: 0.0312 AC XY: 22699 AN XY: 727110

African (AFR) AF: 0.0208 AC: 697 AN: 33478

American (AMR) AF: 0.0194 AC: 866 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0308 AC: 805 AN: 26136

East Asian (EAS) AF: 0.139 AC: 5520 AN: 39700

South Asian (SAS) AF: 0.0500 AC: 4313 AN: 86256

European-Finnish (FIN) AF: 0.0414 AC: 2202 AN: 53190

Middle Eastern (MID) AF: 0.0324 AC: 187 AN: 5768

European-Non Finnish (NFE) AF: 0.0248 AC: 27538 AN: 1111986

Other (OTH) AF: 0.0375 AC: 2267 AN: 60396

GnomAD4 genome AF: 0.0322 AC: 4908 AN: 152386 Hom.: 114 Cov.: 34 AF XY: 0.0339 AC XY: 2528 AN XY: 74524

African (AFR) AF: 0.0219 AC: 910 AN: 41594

American (AMR) AF: 0.0253 AC: 388 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 101 AN: 3472

East Asian (EAS) AF: 0.130 AC: 673 AN: 5192

South Asian (SAS) AF: 0.0586 AC: 283 AN: 4832

European-Finnish (FIN) AF: 0.0417 AC: 443 AN: 10628

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0295 AC: 2007 AN: 68040

Other (OTH) AF: 0.0421 AC: 89 AN: 2114

Alfa AF: 0.0287 Hom.: 38

Bravo AF: 0.0292

Asia WGS AF: 0.0790 AC: 275 AN: 3478

EpiCase AF: 0.0282

EpiControl AF: 0.0290

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 15 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	9.1
DANN	Benign	0.61
PhyloP100		3.9
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: rs1982243; hg19: chr17-78069097; COSMIC: COSV66475277; COSMIC: COSV66475277;