19-48302837-C-T

Position:

• chr19-48302837-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.1097G>A​(p.Arg366His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0328 in 1,613,962 control chromosomes in the GnomAD database, including 1,045 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (65 hom., cov: 32)
  • Exomes 𝑓: 0.034 (980 hom.)
• Consequence: ODAD1 NM_001364171.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.237

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=0.003387034).
• BP6: Variant 19-48302837-C-T is Benign according to our data. Variant chr19-48302837-C-T is described in ClinVar as [Benign]. Clinvar id is 262510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0242 (3692/152298) while in subpopulation NFE AF= 0.0365 (2481/68026). AF 95% confidence interval is 0.0353. There are 65 homozygotes in gnomad4. There are 1742 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 65 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD1	NM_001364171.2	c.1097G>A	p.Arg366His	missense_variant	12/16	ENST00000674294.1
ODAD1	NM_144577.4	c.986G>A	p.Arg329His	missense_variant	10/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD1	ENST00000674294.1	c.1097G>A	p.Arg366His	missense_variant	12/16		NM_001364171.2	P2

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3687 AN: 152180 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.00702

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0330

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.0173

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0365

Gnomad OTH AF: 0.0201

GnomAD3 exomes AF: 0.0255 AC: 6395 AN: 250922 Hom.: 105 AF XY: 0.0251 AC XY: 3398 AN XY: 135624

Gnomad AFR exome AF: 0.00580

Gnomad AMR exome AF: 0.0388

Gnomad ASJ exome AF: 0.0193

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0104

Gnomad FIN exome AF: 0.0180

Gnomad NFE exome AF: 0.0344

Gnomad OTH exome AF: 0.0250

GnomAD4 exome AF: 0.0337 AC: 49224 AN: 1461664 Hom.: 980 Cov.: 34 AF XY: 0.0330 AC XY: 23996 AN XY: 727124

Gnomad4 AFR exome AF: 0.00594

Gnomad4 AMR exome AF: 0.0406

Gnomad4 ASJ exome AF: 0.0199

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.00966

Gnomad4 FIN exome AF: 0.0176

Gnomad4 NFE exome AF: 0.0389

Gnomad4 OTH exome AF: 0.0268

GnomAD4 genome AF: 0.0242 AC: 3692 AN: 152298 Hom.: 65 Cov.: 32 AF XY: 0.0234 AC XY: 1742 AN XY: 74460

Gnomad4 AFR AF: 0.00700

Gnomad4 AMR AF: 0.0332

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.0173

Gnomad4 NFE AF: 0.0365

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.0329 Hom.: 161

Bravo AF: 0.0249

TwinsUK AF: 0.0445 AC: 165

ALSPAC AF: 0.0355 AC: 137

ESP6500AA AF: 0.00704 AC: 31

ESP6500EA AF: 0.0377 AC: 324

ExAC AF: 0.0240 AC: 2915

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.0302

EpiControl AF: 0.0337

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 07, 2016	This alteration is classified as 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. -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 12, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.6
DANN	Benign	0.83
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0048	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.015
Sift	Benign	0.25	T
Sift4G	Benign	0.26	T
Polyphen		0.026	B
Vest4		0.081
MPC		0.31
ClinPred		0.015	T
GERP RS		-1.1
Varity_R		0.027
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs35361179; hg19: chr19-48806094;