rs7252988

Positions:

• chr19-48297081-A-G
• chr19-48297081-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001364171.2(ODAD1):​c.2019T>C​(p.Ser673=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 1,613,386 control chromosomes in the GnomAD database, including 331,731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (27177 hom., cov: 32)
  • Exomes 𝑓: 0.64 (304554 hom.)
• Consequence: ODAD1 NM_001364171.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -8.96

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.1).
• BP6: Variant 19-48297081-A-G is Benign according to our data. Variant chr19-48297081-A-G is described in ClinVar as [Benign]. Clinvar id is 262496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-8.96 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD1	NM_001364171.2	c.2019T>C	p.Ser673=	synonymous_variant	16/16	ENST00000674294.1
ODAD1	NM_144577.4	c.1908T>C	p.Ser636=	synonymous_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD1	ENST00000674294.1	c.2019T>C	p.Ser673=	synonymous_variant	16/16		NM_001364171.2	P2

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89502 AN: 151870 Hom.: 27159 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.598

GnomAD3 exomes AF: 0.563 AC: 141230 AN: 250780 Hom.: 42187 AF XY: 0.570 AC XY: 77263 AN XY: 135658

Gnomad AFR exome AF: 0.523

Gnomad AMR exome AF: 0.391

Gnomad ASJ exome AF: 0.669

Gnomad EAS exome AF: 0.269

Gnomad SAS exome AF: 0.471

Gnomad FIN exome AF: 0.617

Gnomad NFE exome AF: 0.673

Gnomad OTH exome AF: 0.596

GnomAD4 exome AF: 0.638 AC: 931918 AN: 1461398 Hom.: 304554 Cov.: 71 AF XY: 0.633 AC XY: 460424 AN XY: 727046

Gnomad4 AFR exome AF: 0.527

Gnomad4 AMR exome AF: 0.403

Gnomad4 ASJ exome AF: 0.669

Gnomad4 EAS exome AF: 0.253

Gnomad4 SAS exome AF: 0.467

Gnomad4 FIN exome AF: 0.618

Gnomad4 NFE exome AF: 0.679

Gnomad4 OTH exome AF: 0.617

GnomAD4 genome AF: 0.589 AC: 89566 AN: 151988 Hom.: 27177 Cov.: 32 AF XY: 0.581 AC XY: 43151 AN XY: 74280

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.595

Alfa AF: 0.640 Hom.: 35334

Bravo AF: 0.577

Asia WGS AF: 0.359 AC: 1253 AN: 3478

EpiCase AF: 0.667

EpiControl AF: 0.664

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 09, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 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 provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 28, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.022
DANN	Benign	0.36

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: rs7252988; hg19: chr19-48800338; COSMIC: COSV59555559;