rs150259992

chr19-48298077-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS1

The NM_001364171.2(ODAD1):c.1425C>T(p.Asp475=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000722 in 1,613,242 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00069 (7 hom.)
• Consequence: ODAD1 NM_001364171.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.06

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 19-48298077-G-A is Benign according to our data. Variant chr19-48298077-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 241869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.06 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00101 (153/152224) while in subpopulation NFE AF= 0.001 (68/68006). AF 95% confidence interval is 0.000808. There are 0 homozygotes in gnomad4. There are 91 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD1	NM_001364171.2	c.1425C>T	p.Asp475=	synonymous_variant	14/16	ENST00000674294.1
ODAD1	NM_144577.4	c.1314C>T	p.Asp438=	synonymous_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD1	ENST00000674294.1	c.1425C>T	p.Asp475=	synonymous_variant	14/16		NM_001364171.2	P2

Frequencies

GnomAD3 genomes AF: 0.00101 AC: 153 AN: 152108 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000774

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00725

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00100

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00123 AC: 308 AN: 249918 Hom.: 1 AF XY: 0.00126 AC XY: 170 AN XY: 135302

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.000300

Gnomad EAS exome AF: 0.00125

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00830

Gnomad NFE exome AF: 0.000796

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.000692 AC: 1011 AN: 1461018 Hom.: 7 Cov.: 33 AF XY: 0.000703 AC XY: 511 AN XY: 726856

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000135

Gnomad4 ASJ exome AF: 0.000345

Gnomad4 EAS exome AF: 0.000504

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00742

Gnomad4 NFE exome AF: 0.000485

Gnomad4 OTH exome AF: 0.000580

GnomAD4 genome AF: 0.00101 AC: 153 AN: 152224 Hom.: 0 Cov.: 31 AF XY: 0.00122 AC XY: 91 AN XY: 74418

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000775

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00725

Gnomad4 NFE AF: 0.00100

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000941 Hom.: 0

Bravo AF: 0.000393

EpiCase AF: 0.000600

EpiControl AF: 0.000356

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 25, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jan 05, 2019	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. -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.029
Dann	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs150259992; hg19: chr19-48801334; COSMIC: COSV100196517;