17-80090346-A-ACACGGGACGCGCGCAGGCAAGTGCACGAACAACAC

Variant names:

• chr17-80090346-A-ACACGGGACGCGCGCAGGCAAGTGCACGAACAACAC
• rs10693712
• NM_017950.4:c.2832+462_2832+463insCACGGGACGCGCGCAGGCAAGTGCACGAACAACAC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_017950.4(CCDC40):​c.2832+462_2832+463insCACGGGACGCGCGCAGGCAAGTGCACGAACAACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000241 in 414,270 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 0 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: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC40	NM_017950.4	c.2832+462_2832+463insCACGGGACGCGCGCAGGCAAGTGCACGAACAACAC		intron_variant	Intron 17 of 19	ENST00000397545.9	NP_060420.2
CCDC40	NM_001243342.2	c.3040_3041insCACGGGACGCGCGCAGGCAAGTGCACGAACAACAC	p.Arg1014ThrfsTer40	frameshift_variant	Exon 18 of 18		NP_001230271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9	c.2832+462_2832+463insCACGGGACGCGCGCAGGCAAGTGCACGAACAACAC		intron_variant	Intron 17 of 19	5	NM_017950.4	ENSP00000380679.4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000241 AC: 1 AN: 414270 Hom.: 0 Cov.: 43 AF XY: 0.00000475 AC XY: 1 AN XY: 210742

African (AFR) AF: 0.00 AC: 0 AN: 12706

American (AMR) AF: 0.00 AC: 0 AN: 17058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7698

East Asian (EAS) AF: 0.00 AC: 0 AN: 15784

South Asian (SAS) AF: 0.00 AC: 0 AN: 29056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1824

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 295318

Other (OTH) AF: 0.0000517 AC: 1 AN: 19344

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.018

Splicing

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

Other links and lift over

dbSNP: rs10693712; hg19: chr17-78064145;