19-48306328-G-T

Variant names:

• chr19-48306328-G-T
• rs10416590
• NM_001364171.2:c.598-5C>A

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.598-5C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00434 in 1,550,312 control chromosomes in the GnomAD database, including 245 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (137 hom., cov: 31)
  • Exomes 𝑓: 0.0024 (108 hom.)
• Consequence: ODAD1 NM_001364171.2 splice_region, intron
• Scores: Splicing: ADA: 0.00008102
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -3.34
• Publications: 3 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: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• 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=-0.84).
• BP6: Variant 19-48306328-G-T is Benign according to our data. Variant chr19-48306328-G-T is described in ClinVar as Benign. ClinVar VariationId is 262500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0763 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.598-5C>A		splice_region intron	N/A	NP_001351100.1	A0A6I8PTZ2
	ODAD1	NM_144577.4		c.487-5C>A		splice_region intron	N/A	NP_653178.3	Q96M63-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD1	ENST00000674294.1	MANE Select	c.598-5C>A		splice_region intron	N/A	ENSP00000501363.1	A0A6I8PTZ2
	ODAD1	ENST00000315396.7	TSL:1	c.487-5C>A		splice_region intron	N/A	ENSP00000318429.7	Q96M63-1
	ODAD1	ENST00000859784.1		c.598-5C>A		splice_region intron	N/A	ENSP00000529843.1

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3417 AN: 151996 Hom.: 136 Cov.: 31

Gnomad AFR AF: 0.0784

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00872

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00539 AC: 833 AN: 154490 AF XY: 0.00421

Gnomad AFR exome AF: 0.0843

Gnomad AMR exome AF: 0.00478

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000417

Gnomad OTH exome AF: 0.00414

GnomAD4 exome AF: 0.00235 AC: 3292 AN: 1398198 Hom.: 108 Cov.: 30 AF XY: 0.00209 AC XY: 1441 AN XY: 689702

African (AFR) AF: 0.0832 AC: 2627 AN: 31566

American (AMR) AF: 0.00504 AC: 180 AN: 35690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25158

East Asian (EAS) AF: 0.00 AC: 0 AN: 35706

South Asian (SAS) AF: 0.000114 AC: 9 AN: 79204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49234

Middle Eastern (MID) AF: 0.00474 AC: 27 AN: 5694

European-Non Finnish (NFE) AF: 0.000168 AC: 181 AN: 1078000

Other (OTH) AF: 0.00462 AC: 268 AN: 57946

GnomAD4 genome AF: 0.0226 AC: 3433 AN: 152114 Hom.: 137 Cov.: 31 AF XY: 0.0223 AC XY: 1657 AN XY: 74354

African (AFR) AF: 0.0785 AC: 3257 AN: 41480

American (AMR) AF: 0.00871 AC: 133 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 67984

Other (OTH) AF: 0.0132 AC: 28 AN: 2114

Alfa AF: 0.00576 Hom.: 42

Bravo AF: 0.0252

Asia WGS AF: 0.00462 AC: 17 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia (2)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia 20 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.024
DANN	Benign	0.50
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000081
dbscSNV1_RF	Benign	0.010
SpliceAI score (max)		0.020		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: rs10416590; hg19: chr19-48809585;