17-41935240-C-G

Variant names:

• chr17-41935240-C-G
• rs1197824633
• NM_031421.5:c.138C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_031421.5(ODAD4):​c.138C>G​(p.Asp46Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ODAD4 NM_031421.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.797
• Publications: 0 publications found

Genes affected

ODAD4 (HGNC:25280): (outer dynein arm docking complex subunit 4) This gene encodes a tetratricopeptide repeat domain-containing protein that localizes to ciliary axonmenes and plays a role in the docking of the outer dynein arm to cilia. Mutations in this gene cause severely reduced ciliary motility and the disorder CILD35 (ciliary dyskinesia,primary, 35). Primary ciliary dyskinesia is often associated with recurrent respiratory infections, immotile spermatozoa, and situs inversus; an inversion in left-right body symmetry. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2017]

ODAD4 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 35

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031421.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD4	NM_031421.5	MANE Select	c.138C>G	p.Asp46Glu	missense	Exon 2 of 12	NP_113609.1	Q96NG3-1
	ODAD4	NM_001350319.2		c.138C>G	p.Asp46Glu	missense	Exon 2 of 11	NP_001337248.1
	ODAD4	NR_110662.3		n.245C>G		non_coding_transcript_exon	Exon 2 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD4	ENST00000377540.6	TSL:1 MANE Select	c.138C>G	p.Asp46Glu	missense	Exon 2 of 12	ENSP00000478589.1	Q96NG3-1
	ODAD4	ENST00000918348.1		c.138C>G	p.Asp46Glu	missense	Exon 2 of 10	ENSP00000588407.1
	ODAD4	ENST00000918347.1		c.138C>G	p.Asp46Glu	missense	Exon 2 of 8	ENSP00000588406.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.078	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.67	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.59	T
PhyloP100		-0.80
PrimateAI	Uncertain	0.51	T
REVEL	Benign	0.29
Sift4G	Benign	0.067	T
Polyphen		0.82	P
Vest4		0.63
MutPred		0.58		Gain of ubiquitination at K47 (P = 0.0828)
MVP		0.20
ClinPred		0.97	D
GERP RS		-3.0
Varity_R		0.24
gMVP		0.28

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

Other links and lift over

dbSNP: rs1197824633; hg19: chr17-40091493;