NM_001364171.2:c.522G>A

Variant names:

• chr19-48311628-C-T
• rs200360777
• NM_001364171.2:c.522G>A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2 BP4_Strong BP6_Very_Strong BP7 BS1

The NM_001364171.2(ODAD1):​c.522G>A​(p.Ala174Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000928 in 1,551,164 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00078 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00094 (1 hom.)
• Consequence: ODAD1 NM_001364171.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.15

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 Benign. Variant got -15 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 19-48311628-C-T is Benign according to our data. Variant chr19-48311628-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 454971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.15 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000775 (118/152210) while in subpopulation NFE AF= 0.00132 (90/68008). AF 95% confidence interval is 0.0011. There are 0 homozygotes in gnomad4. There are 53 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD1	NM_001364171.2	c.522G>A	p.Ala174Ala	synonymous_variant	Exon 7 of 16	ENST00000674294.1	NP_001351100.1
ODAD1	NM_144577.4	c.411G>A	p.Ala137Ala	synonymous_variant	Exon 5 of 14		NP_653178.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD1	ENST00000674294.1	c.522G>A	p.Ala174Ala	synonymous_variant	Exon 7 of 16		NM_001364171.2	ENSP00000501363.1

Frequencies

GnomAD3 genomes AF: 0.000776 AC: 118 AN: 152092 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00132

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000941 AC: 147 AN: 156202 Hom.: 0 AF XY: 0.00115 AC XY: 95 AN XY: 82794

Gnomad AFR exome AF: 0.000379

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.00471

Gnomad EAS exome AF: 0.000275

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000603

Gnomad NFE exome AF: 0.00144

Gnomad OTH exome AF: 0.000684

GnomAD4 exome AF: 0.000945 AC: 1322 AN: 1398954 Hom.: 1 Cov.: 30 AF XY: 0.000951 AC XY: 656 AN XY: 690024

Gnomad4 AFR exome AF: 0.000158

Gnomad4 AMR exome AF: 0.000392

Gnomad4 ASJ exome AF: 0.00453

Gnomad4 EAS exome AF: 0.000420

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000142

Gnomad4 NFE exome AF: 0.00103

Gnomad4 OTH exome AF: 0.000914

GnomAD4 genome AF: 0.000775 AC: 118 AN: 152210 Hom.: 0 Cov.: 31 AF XY: 0.000712 AC XY: 53 AN XY: 74416

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00132

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00116 Hom.: 0

Bravo AF: 0.000774

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:2

Feb 06, 2017

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Aug 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ODAD1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.068
DANN	Benign	0.74

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: rs200360777; hg19: chr19-48814885;