rs147072026

Positions:

• chr19-48297312-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.1788C>T​(p.His596His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00644 in 1,613,628 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0067 (45 hom.)
• Consequence: ODAD1 NM_001364171.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.48

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 19-48297312-G-A is Benign according to our data. Variant chr19-48297312-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 241875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.48 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00436 (664/152324) while in subpopulation NFE AF= 0.00787 (535/68010). AF 95% confidence interval is 0.00732. There are 1 homozygotes in gnomad4. There are 273 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAD1	NM_001364171.2	c.1788C>T	p.His596His	synonymous_variant	16/16	ENST00000674294.1	NP_001351100.1
ODAD1	NM_144577.4	c.1677C>T	p.His559His	synonymous_variant	14/14		NP_653178.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD1	ENST00000674294.1	c.1788C>T	p.His596His	synonymous_variant	16/16		NM_001364171.2	ENSP00000501363.1

Frequencies

GnomAD3 genomes AF: 0.00436 AC: 664 AN: 152206 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00200

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00787

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00384 AC: 964 AN: 250800 Hom.: 3 AF XY: 0.00392 AC XY: 532 AN XY: 135664

Gnomad AFR exome AF: 0.00197

Gnomad AMR exome AF: 0.000752

Gnomad ASJ exome AF: 0.000596

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000523

Gnomad FIN exome AF: 0.00170

Gnomad NFE exome AF: 0.00724

Gnomad OTH exome AF: 0.00408

GnomAD4 exome AF: 0.00666 AC: 9730 AN: 1461304 Hom.: 45 Cov.: 62 AF XY: 0.00651 AC XY: 4734 AN XY: 727002

Gnomad4 AFR exome AF: 0.00134

Gnomad4 AMR exome AF: 0.000939

Gnomad4 ASJ exome AF: 0.000536

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000765

Gnomad4 FIN exome AF: 0.00238

Gnomad4 NFE exome AF: 0.00823

Gnomad4 OTH exome AF: 0.00460

GnomAD4 genome AF: 0.00436 AC: 664 AN: 152324 Hom.: 1 Cov.: 33 AF XY: 0.00367 AC XY: 273 AN XY: 74482

Gnomad4 AFR AF: 0.00200

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00787

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00553 Hom.: 2

Bravo AF: 0.00436

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Sep 14, 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. -

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	ODAD1: BP4, BP7, BS2 -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.044
DANN	Benign	0.72

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: rs147072026; hg19: chr19-48800569;