17-80090346-A-ACACGGGACGCGCGCAGGCACGTGCACGAACAACAC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_017950.4(CCDC40):c.2832+462_2832+463insCACGGGACGCGCGCAGGCACGTGCACGAACAACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000052 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000094 (9 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC40	NM_017950.4	c.2832+462_2832+463insCACGGGACGCGCGCAGGCACGTGCACGAACAACAC		intron_variant		ENST00000397545.9
CCDC40	NM_001243342.2	c.3040_3041insCACGGGACGCGCGCAGGCACGTGCACGAACAACAC	p.Arg1014ThrfsTer40	frameshift_variant	18/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC40	ENST00000397545.9	c.2832+462_2832+463insCACGGGACGCGCGCAGGCACGTGCACGAACAACAC		intron_variant		5	NM_017950.4	P2

Frequencies

GnomAD3 genomes AF: 0.0000517 AC: 1 AN: 19356 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000138

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000354 AC: 23 AN: 65002 Hom.: 8 AF XY: 0.000339 AC XY: 12 AN XY: 35428

Gnomad AFR exome AF: 0.000843

Gnomad AMR exome AF: 0.000153

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00199

Gnomad SAS exome AF: 0.000170

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000218

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000941 AC: 39 AN: 414252 Hom.: 9 Cov.: 43 AF XY: 0.000109 AC XY: 23 AN XY: 210730

Gnomad4 AFR exome AF: 0.000315

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000130

Gnomad4 EAS exome AF: 0.0000634

Gnomad4 SAS exome AF: 0.000172

Gnomad4 FIN exome AF: 0.000194

Gnomad4 NFE exome AF: 0.0000813

Gnomad4 OTH exome AF: 0.0000517

GnomAD4 genome AF: 0.0000517 AC: 1 AN: 19356 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 9544

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000138

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10693712; hg19: chr17-78064145;