17-80089837-G-C

Variant names:

• chr17-80089837-G-C
• NM_017950.4:c.2785G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_017950.4(CCDC40):​c.2785G>C​(p.Gly929Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC40 NM_017950.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.56

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.75

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC40	NM_017950.4	c.2785G>C	p.Gly929Arg	missense_variant	Exon 17 of 20	ENST00000397545.9	NP_060420.2
CCDC40	NM_001243342.2	c.2785G>C	p.Gly929Arg	missense_variant	Exon 17 of 18		NP_001230271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9	c.2785G>C	p.Gly929Arg	missense_variant	Exon 17 of 20	5	NM_017950.4	ENSP00000380679.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461848 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	.;D
Eigen	Uncertain	0.38
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.75	D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-6.9	D;D
REVEL	Benign	0.19
Sift	Uncertain	0.0030	D;D
Sift4G	Benign	0.085	T;T
Polyphen		1.0	.;D
Vest4		0.59
MutPred		0.20		Gain of MoRF binding (P = 0.0141);Gain of MoRF binding (P = 0.0141);
MVP		0.69
MPC		0.50
ClinPred		0.96	D
GERP RS		3.4
Varity_R		0.47
gMVP		0.51

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-78063636;