19-48296734-C-T

Variant names:

• chr19-48296734-C-T
• rs10413640
• NM_001364171.2:c.*242G>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.*242G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,355,628 control chromosomes in the GnomAD database, including 739 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (418 hom., cov: 32)
  • Exomes 𝑓: 0.0074 (321 hom.)
• Consequence: ODAD1 NM_001364171.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.02
• Publications: 2 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=-0.83).
• BP6: Variant 19-48296734-C-T is Benign according to our data. Variant chr19-48296734-C-T is described in ClinVar as [Benign]. Clinvar id is 1247134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD1	NM_001364171.2	c.*242G>A		3_prime_UTR_variant	Exon 16 of 16	ENST00000674294.1	NP_001351100.1
ODAD1	NM_144577.4	c.*242G>A		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.*242G>A		3_prime_UTR_variant	Exon 16 of 16		NM_001364171.2	ENSP00000501363.1

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 6394 AN: 151930 Hom.: 417 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.000284

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00396

Gnomad OTH AF: 0.0283

GnomAD4 exome AF: 0.00741 AC: 8923 AN: 1203580 Hom.: 321 Cov.: 24 AF XY: 0.00723 AC XY: 4186 AN XY: 579214

African (AFR) AF: 0.149 AC: 3815 AN: 25588

American (AMR) AF: 0.0103 AC: 134 AN: 12966

Ashkenazi Jewish (ASJ) AF: 0.00228 AC: 39 AN: 17104

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30166

South Asian (SAS) AF: 0.00836 AC: 413 AN: 49390

European-Finnish (FIN) AF: 0.000369 AC: 10 AN: 27094

Middle Eastern (MID) AF: 0.0130 AC: 44 AN: 3396

European-Non Finnish (NFE) AF: 0.00395 AC: 3900 AN: 988260

Other (OTH) AF: 0.0114 AC: 567 AN: 49616

GnomAD4 genome AF: 0.0422 AC: 6411 AN: 152048 Hom.: 418 Cov.: 32 AF XY: 0.0414 AC XY: 3076 AN XY: 74312

African (AFR) AF: 0.140 AC: 5787 AN: 41410

American (AMR) AF: 0.0149 AC: 228 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0106 AC: 51 AN: 4816

European-Finnish (FIN) AF: 0.000284 AC: 3 AN: 10578

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00396 AC: 269 AN: 68000

Other (OTH) AF: 0.0280 AC: 59 AN: 2110

Alfa AF: 0.00781 Hom.: 11

Bravo AF: 0.0466

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 25, 2019

GeneDx

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	-0.83
CADD	Benign	1.2
DANN	Benign	0.42
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10413640; hg19: chr19-48799991;