19-48303764-C-T

Position:

• chr19-48303764-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001364171.2(ODAD1):​c.874G>A​(p.Val292Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,611,328 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (2 hom.)
• Consequence: ODAD1 NM_001364171.2 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0220

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 (MetaRNN=0.0057453513).
• BP6: Variant 19-48303764-C-T is Benign according to our data. Variant chr19-48303764-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 574685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-48303764-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000158 (24/152352) while in subpopulation EAS AF= 0.00251 (13/5184). AF 95% confidence interval is 0.00148. There are 0 homozygotes in gnomad4. There are 16 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAD1	NM_001364171.2	c.874G>A	p.Val292Ile	missense_variant	10/16	ENST00000674294.1	NP_001351100.1
ODAD1	NM_144577.4	c.763G>A	p.Val255Ile	missense_variant	8/14		NP_653178.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD1	ENST00000674294.1	c.874G>A	p.Val292Ile	missense_variant	10/16		NM_001364171.2	ENSP00000501363.1

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152234 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000274 AC: 68 AN: 247812 Hom.: 0 AF XY: 0.000269 AC XY: 36 AN XY: 133956

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000293

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00278

Gnomad SAS exome AF: 0.000530

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000134 AC: 195 AN: 1458976 Hom.: 2 Cov.: 34 AF XY: 0.000153 AC XY: 111 AN XY: 725740

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000226

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00234

Gnomad4 SAS exome AF: 0.000663

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000243

Gnomad4 OTH exome AF: 0.000282

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152352 Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16 AN XY: 74498

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000473

Bravo AF: 0.000200

ExAC AF: 0.000239 AC: 29

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	May 02, 2022	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 18, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.84
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.0057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.014
Sift	Benign	0.19	T
Sift4G	Benign	0.23	T
Polyphen		0.16	B
Vest4		0.057
MutPred		0.23		Loss of disorder (P = 0.093);
MVP		0.38
MPC		0.17
ClinPred		0.012	T
GERP RS		0.68
Varity_R		0.028
gMVP		0.055

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

Publications

LitVar

Other links and lift over

dbSNP: rs571330368; hg19: chr19-48807021; COSMIC: COSV59555502; COSMIC: COSV59555502;