rs201042940

Positions:

• chr17-80048756-G-A
• chr17-80048756-G-C
• chr17-80048756-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017950.4(CCDC40):​c.850G>A​(p.Asp284Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D284H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CCDC40 NM_017950.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.526

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23984027).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC40	NM_017950.4	c.850G>A	p.Asp284Asn	missense_variant	5/20	ENST00000397545.9
CCDC40	NM_001243342.2	c.850G>A	p.Asp284Asn	missense_variant	5/18
CCDC40	NM_001330508.2	c.850G>A	p.Asp284Asn	missense_variant	5/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC40	ENST00000397545.9	c.850G>A	p.Asp284Asn	missense_variant	5/20	5	NM_017950.4	P2
	ENST00000695611.1	n.1432-1237C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000425 AC: 1 AN: 235048 Hom.: 0 AF XY: 0.00000782 AC XY: 1 AN XY: 127810

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000952

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	14
DANN	Uncertain	1.0
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.81	T;T;T;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.3	M;M;M;M
MutationTaster	Benign	0.74	N;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.6	D;D;D;D
REVEL	Benign	0.061
Sift	Benign	0.23	T;T;T;D
Sift4G	Benign	0.089	T;T;T;D
Polyphen		0.62, 0.70	.;P;.;P
Vest4		0.32
MutPred		0.38		Gain of MoRF binding (P = 0.1513);Gain of MoRF binding (P = 0.1513);Gain of MoRF binding (P = 0.1513);Gain of MoRF binding (P = 0.1513);
MVP		0.51
MPC		0.27
ClinPred		0.92	D
GERP RS		1.6
Varity_R		0.10
gMVP		0.087

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

LitVar

Other links and lift over

dbSNP: rs201042940; hg19: chr17-78022555;