rs34628933

chr19-48303981-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001364171.2(ODAD1):c.825C>T(p.Pro275=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00533 in 1,614,142 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (27 hom., cov: 33)
  • Exomes 𝑓: 0.0047 (52 hom.)
• Consequence: ODAD1 NM_001364171.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.633

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-48303981-G-A is Benign according to our data. Variant chr19-48303981-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 241880.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.633 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0112 (1709/152322) while in subpopulation AFR AF= 0.0317 (1318/41584). AF 95% confidence interval is 0.0303. There are 27 homozygotes in gnomad4. There are 820 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD1	NM_001364171.2	c.825C>T	p.Pro275=	synonymous_variant	9/16	ENST00000674294.1
ODAD1	NM_144577.4	c.714C>T	p.Pro238=	synonymous_variant	7/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD1	ENST00000674294.1	c.825C>T	p.Pro275=	synonymous_variant	9/16		NM_001364171.2	P2
ODAD1	ENST00000315396.7	c.714C>T	p.Pro238=	synonymous_variant	7/14	1		A2
ODAD1	ENST00000474199.6	c.825C>T	p.Pro275=	synonymous_variant	9/15	2		A2
ODAD1	ENST00000674207.1	c.*533C>T		3_prime_UTR_variant, NMD_transcript_variant	7/13

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1707 AN: 152204 Hom.: 27 Cov.: 33

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0103

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00368

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00599 AC: 1506 AN: 251296 Hom.: 17 AF XY: 0.00601 AC XY: 817 AN XY: 135832

Gnomad AFR exome AF: 0.0328

Gnomad AMR exome AF: 0.00257

Gnomad ASJ exome AF: 0.00258

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00931

Gnomad FIN exome AF: 0.000601

Gnomad NFE exome AF: 0.00474

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.00472 AC: 6902 AN: 1461820 Hom.: 52 Cov.: 33 AF XY: 0.00485 AC XY: 3525 AN XY: 727210

Gnomad4 AFR exome AF: 0.0336

Gnomad4 AMR exome AF: 0.00259

Gnomad4 ASJ exome AF: 0.00256

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00945

Gnomad4 FIN exome AF: 0.000505

Gnomad4 NFE exome AF: 0.00393

Gnomad4 OTH exome AF: 0.00556

GnomAD4 genome AF: 0.0112 AC: 1709 AN: 152322 Hom.: 27 Cov.: 33 AF XY: 0.0110 AC XY: 820 AN XY: 74486

Gnomad4 AFR AF: 0.0317

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0106

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00368

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00805 Hom.: 1

Bravo AF: 0.0119

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.00409

EpiControl AF: 0.00551

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:2

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Nov 18, 2016	This alteration is classified as 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. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.58
Dann	Benign	0.54

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: rs34628933; hg19: chr19-48807238;