19-48296961-T-C

Variant names:

• chr19-48296961-T-C
• rs10415825
• NM_001364171.2:c.*15A>G

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.*15A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,569,652 control chromosomes in the GnomAD database, including 31,752 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3872 hom., cov: 31)
  • Exomes 𝑓: 0.19 (27880 hom.)
• Consequence: ODAD1 NM_001364171.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.87
• Publications: 9 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=-0.91).
• BP6: Variant 19-48296961-T-C is Benign according to our data. Variant chr19-48296961-T-C is described in ClinVar as [Benign]. Clinvar id is 262481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD1	NM_001364171.2	c.*15A>G		3_prime_UTR_variant	Exon 16 of 16	ENST00000674294.1	NP_001351100.1
ODAD1	NM_144577.4	c.*15A>G		3_prime_UTR_variant	Exon 14 of 14		NP_653178.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD1	ENST00000674294.1	c.*15A>G		3_prime_UTR_variant	Exon 16 of 16		NM_001364171.2	ENSP00000501363.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33195 AN: 151806 Hom.: 3868 Cov.: 31

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.191

GnomAD2 exomes AF: 0.184 AC: 39530 AN: 215070 AF XY: 0.187

Gnomad AFR exome AF: 0.285

Gnomad AMR exome AF: 0.0863

Gnomad ASJ exome AF: 0.189

Gnomad EAS exome AF: 0.123

Gnomad FIN exome AF: 0.251

Gnomad NFE exome AF: 0.199

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.194 AC: 275149 AN: 1417728 Hom.: 27880 Cov.: 32 AF XY: 0.194 AC XY: 136349 AN XY: 701862

African (AFR) AF: 0.290 AC: 9387 AN: 32356

American (AMR) AF: 0.0917 AC: 3701 AN: 40368

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 4429 AN: 23340

East Asian (EAS) AF: 0.114 AC: 4502 AN: 39330

South Asian (SAS) AF: 0.183 AC: 14811 AN: 80796

European-Finnish (FIN) AF: 0.249 AC: 11618 AN: 46716

Middle Eastern (MID) AF: 0.178 AC: 720 AN: 4044

European-Non Finnish (NFE) AF: 0.197 AC: 215069 AN: 1092350

Other (OTH) AF: 0.187 AC: 10912 AN: 58428

GnomAD4 genome AF: 0.219 AC: 33219 AN: 151924 Hom.: 3872 Cov.: 31 AF XY: 0.221 AC XY: 16400 AN XY: 74266

African (AFR) AF: 0.289 AC: 11987 AN: 41444

American (AMR) AF: 0.128 AC: 1952 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 665 AN: 3472

East Asian (EAS) AF: 0.125 AC: 645 AN: 5172

South Asian (SAS) AF: 0.189 AC: 904 AN: 4778

European-Finnish (FIN) AF: 0.261 AC: 2764 AN: 10584

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13712 AN: 67888

Other (OTH) AF: 0.192 AC: 404 AN: 2108

Alfa AF: 0.181 Hom.: 922

Bravo AF: 0.211

Asia WGS AF: 0.161 AC: 562 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.022
DANN	Benign	0.53
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10415825; hg19: chr19-48800218;