19-48318739-T-G

Variant names:

• chr19-48318739-T-G
• rs377679653
• NM_001364171.2:c.144A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001364171.2(ODAD1):​c.144A>C​(p.Glu48Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E48E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ODAD1 NM_001364171.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• Publications: 0 publications found

Genes affected

ODAD1 (HGNC:26560): (outer dynein arm docking complex subunit 1) This gene encodes a coiled-coil domain-containing protein that is a component of the outer dynein arm docking complex in cilia cells. Mutations in this gene may cause primary ciliary dyskinesia 20. [provided by RefSeq, May 2013]

ODAD1 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 20

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17818713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD1	NM_001364171.2	c.144A>C	p.Glu48Asp	missense_variant	Exon 4 of 16	ENST00000674294.1	NP_001351100.1
ODAD1	NM_144577.4	c.33A>C	p.Glu11Asp	missense_variant	Exon 2 of 14		NP_653178.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD1	ENST00000674294.1	c.144A>C	p.Glu48Asp	missense_variant	Exon 4 of 16		NM_001364171.2	ENSP00000501363.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399022 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 690056

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.00 AC: 0 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078658

Other (OTH) AF: 0.00 AC: 0 AN: 57998

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0084	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-2.0
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.10
Sift	Uncertain	0.018	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.28
MutPred		0.18		Loss of ubiquitination at K10 (P = 0.0777);
MVP		0.24
MPC		0.73
ClinPred		0.95	D
GERP RS		-4.0
Varity_R		0.25
gMVP		0.42
Mutation Taster		=92/8	polymorphism

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: rs377679653; hg19: chr19-48821996;