rs73942222

chr19-48303782-C-Gchr19-48303782-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001364171.2(ODAD1):c.856G>C(p.Gly286Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ODAD1 NM_001364171.2 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.022407144).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD1	NM_001364171.2	c.856G>C	p.Gly286Arg	missense_variant, splice_region_variant	10/16	ENST00000674294.1
ODAD1	NM_144577.4	c.745G>C	p.Gly249Arg	missense_variant, splice_region_variant	8/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD1	ENST00000674294.1	c.856G>C	p.Gly286Arg	missense_variant, splice_region_variant	10/16		NM_001364171.2	P2
ODAD1	ENST00000315396.7	c.745G>C	p.Gly249Arg	missense_variant, splice_region_variant	8/14	1		A2
ODAD1	ENST00000474199.6	c.856G>C	p.Gly286Arg	missense_variant, splice_region_variant	10/15	2		A2
ODAD1	ENST00000674207.1	c.*564G>C		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	8/13

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000823 AC: 2 AN: 243150 Hom.: 0 AF XY: 0.00000762 AC XY: 1 AN XY: 131182

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000296

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: 0.00000912

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1454500 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 723192

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000227

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.036
Dann	Benign	0.74
DEOGEN2	Benign	0.00014	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.3	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.012
Sift	Benign	0.59	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.030
MutPred		0.23		Gain of MoRF binding (P = 0.0381);
MVP		0.21
MPC		0.24
ClinPred		0.023	T
GERP RS		-2.6
Varity_R		0.049
gMVP		0.083

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: rs73942222; hg19: chr19-48807039;