rs12952612

Variant names:

• chr17-80097253-T-A
• rs12952612
• NM_017950.4:c.3030T>A

Your query was ambiguous. Multiple possible variants found:

• chr17-80097253-T-A
• chr17-80097253-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017950.4(CCDC40):​c.3030T>A​(p.Asp1010Glu) 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. 16/22 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. D1010N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC40 NM_017950.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• Publications: 29 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.016174018).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC40	NM_017950.4	c.3030T>A	p.Asp1010Glu	missense_variant	Exon 19 of 20	ENST00000397545.9	NP_060420.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9	c.3030T>A	p.Asp1010Glu	missense_variant	Exon 19 of 20	5	NM_017950.4	ENSP00000380679.4
CCDC40	ENST00000574799.5	n.2567T>A		non_coding_transcript_exon_variant	Exon 15 of 16	1
CCDC40	ENST00000572253.5	n.3281T>A		non_coding_transcript_exon_variant	Exon 6 of 6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 86886

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.51
DANN	Benign	0.52
DEOGEN2	Benign	0.027	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.7	N
PhyloP100		-0.37
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.073
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.051
ClinPred		0.030	T
GERP RS		-1.2
Varity_R		0.030
gMVP		0.028
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs12952612; hg19: chr17-78071052;