Genetic Variant ODAD1:p.Pro697Gln (chr19-48297010-G-T) – 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.2090C>A(p.Pro697Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,344 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. 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. P697L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ODAD1
NM_001364171.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.27

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=0.062864035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD1	NM_001364171.2 link	c.2090C>A	p.Pro697Gln	missense_variant	Exon 16 of 16	ENST00000674294.1	NP_001351100.1
ODAD1	NM_144577.4 link	c.1979C>A	p.Pro660Gln	missense_variant	Exon 14 of 14		NP_653178.3	Q96M63-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD1	ENST00000674294.1 link	c.2090C>A	p.Pro697Gln	missense_variant	Exon 16 of 16		NM_001364171.2	ENSP00000501363.1		A0A6I8PTZ2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457344

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725002

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:

33434

American (AMR)

AF:

0.00

AC:

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25884

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86026

European-Finnish (FIN)

AF:

0.0000195

AC:

AN:

51364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5078

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111026

Other (OTH)

AF:

0.00

AC:

AN:

60208

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), 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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.0

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0041

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.42

M_CAP

Benign

0.027

MetaRNN

Benign

0.063

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

-1.3

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.8

REVEL

Benign

0.033

Sift

Benign

0.34

Sift4G

Benign

0.28

Polyphen

0.22

Vest4

0.14

MutPred

0.17

Loss of glycosylation at P660 (P = 0.0211);

MVP

0.17

MPC

0.74

ClinPred

0.13

GERP RS

-1.4

Varity_R

0.033

gMVP

0.099

Mutation Taster

=98/2

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over