rs2292113

Variant names:

• chr19-48297534-A-G
• rs2292113
• NM_001364171.2:c.1582-16T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001364171.2(ODAD1):​c.1582-16T>C variant causes a 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 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.109
• Publications: 15 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364171.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD1	NM_001364171.2	MANE Select	c.1582-16T>C		intron	N/A	NP_001351100.1
	ODAD1	NM_144577.4		c.1471-16T>C		intron	N/A	NP_653178.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD1	ENST00000674294.1	MANE Select	c.1582-16T>C		intron	N/A	ENSP00000501363.1
	ODAD1	ENST00000315396.7	TSL:1	c.1471-16T>C		intron	N/A	ENSP00000318429.7
	ODAD1	ENST00000474199.6	TSL:2	c.1637T>C	p.Val546Ala	missense	Exon 15 of 15	ENSP00000501357.1

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

GnomAD2 exomes AF: 0.319 AC: 69275 AN: 217314 AF XY: 0.324

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 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

African (AFR) AF: 0.489 AC: 16143 AN: 32982

American (AMR) AF: 0.188 AC: 7908 AN: 42130

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 11201 AN: 25320

East Asian (EAS) AF: 0.115 AC: 4486 AN: 39090

South Asian (SAS) AF: 0.297 AC: 24986 AN: 84186

European-Finnish (FIN) AF: 0.329 AC: 17026 AN: 51702

Middle Eastern (MID) AF: 0.393 AC: 2247 AN: 5712

European-Non Finnish (NFE) AF: 0.372 AC: 410350 AN: 1103136

Other (OTH) AF: 0.356 AC: 21249 AN: 59638

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

African (AFR) AF: 0.479 AC: 19852 AN: 41404

American (AMR) AF: 0.265 AC: 4050 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1543 AN: 3470

East Asian (EAS) AF: 0.125 AC: 644 AN: 5138

South Asian (SAS) AF: 0.286 AC: 1378 AN: 4810

European-Finnish (FIN) AF: 0.333 AC: 3525 AN: 10570

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.372 AC: 25239 AN: 67830

Other (OTH) AF: 0.368 AC: 776 AN: 2110

Alfa AF: 0.387 Hom.: 2192

Bravo AF: 0.377

Asia WGS AF: 0.220 AC: 769 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	8.0
DANN	Benign	0.38
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2292113; hg19: chr19-48800791; COSMIC: COSV59555161;