dbSNP rs73942222: ODAD1:p.Gly286Trp (chr19-48303782-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001364171.2(ODAD1):c.856G>T(p.Gly286Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. G286R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ODAD1
NM_001364171.2 missense, splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.916

Publications

0 publications found

Variant links:

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

ODAD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.040400833).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364171.2. 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
	ODAD1	NM_001364171.2	MANE Select	c.856G>T	p.Gly286Trp	missense splice_region	Exon 10 of 16	NP_001351100.1
	ODAD1	NM_144577.4		c.745G>T	p.Gly249Trp	missense splice_region	Exon 8 of 14	NP_653178.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ODAD1	ENST00000674294.1	MANE Select	c.856G>T	p.Gly286Trp	missense splice_region	Exon 10 of 16	ENSP00000501363.1
ODAD1	ENST00000315396.7	TSL:1	c.745G>T	p.Gly249Trp	missense splice_region	Exon 8 of 14	ENSP00000318429.7
ODAD1	ENST00000859784.1		c.856G>T	p.Gly286Trp	missense splice_region	Exon 9 of 15	ENSP00000529843.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454500

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723192

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33418

American (AMR)

AF:

0.00

AC:

AN:

44000

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25292

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000118

AC:

AN:

85090

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53070

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108140

Other (OTH)

AF:

0.00

AC:

AN:

60082

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.6

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.0041

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0050

LIST_S2

Benign

0.17

M_CAP

Benign

0.028

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.41

PhyloP100

-0.92

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.61

REVEL

Benign

0.014

Sift

Benign

0.067

Sift4G

Uncertain

0.031

Polyphen

0.0010

Vest4

0.17

MutPred

0.31

Loss of disorder (P = 0.0081)

MVP

0.17

MPC

0.24

ClinPred

0.046

GERP RS

-2.6

Varity_R

0.042

gMVP

0.13

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over