rs2292113

chr19-48297534-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001364171.2(ODAD1):c.1582-16T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,595,706 control chromosomes in the GnomAD database, including 106,701 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11386 hom., cov: 31)
  • Exomes 𝑓: 0.36 (95315 hom.)
• Consequence: ODAD1 NM_001364171.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.109

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 19-48297534-A-G is Benign according to our data. Variant chr19-48297534-A-G is described in ClinVar as [Benign]. Clinvar id is 262490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD1	NM_001364171.2	c.1582-16T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000674294.1
ODAD1	NM_144577.4	c.1471-16T>C		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD1	ENST00000674294.1	c.1582-16T>C		splice_polypyrimidine_tract_variant, intron_variant			NM_001364171.2	P2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57281 AN: 151694 Hom.: 11365 Cov.: 31

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.369

GnomAD3 exomes AF: 0.319 AC: 69275 AN: 217314 Hom.: 11933 AF XY: 0.324 AC XY: 38244 AN XY: 118160

Gnomad AFR exome AF: 0.477

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.438

Gnomad EAS exome AF: 0.125

Gnomad SAS exome AF: 0.298

Gnomad FIN exome AF: 0.331

Gnomad NFE exome AF: 0.369

Gnomad OTH exome AF: 0.334

GnomAD4 exome AF: 0.357 AC: 515596 AN: 1443896 Hom.: 95315 Cov.: 57 AF XY: 0.355 AC XY: 254917 AN XY: 717206

Gnomad4 AFR exome AF: 0.489

Gnomad4 AMR exome AF: 0.188

Gnomad4 ASJ exome AF: 0.442

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.297

Gnomad4 FIN exome AF: 0.329

Gnomad4 NFE exome AF: 0.372

Gnomad4 OTH exome AF: 0.356

GnomAD4 genome AF: 0.378 AC: 57341 AN: 151810 Hom.: 11386 Cov.: 31 AF XY: 0.371 AC XY: 27538 AN XY: 74192

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.368

Alfa AF: 0.385 Hom.: 2104

Bravo AF: 0.377

Asia WGS AF: 0.220 AC: 769 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	8.0
Dann	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2292113; hg19: chr19-48800791; COSMIC: COSV59555161;