rs114554656

Variant names:

• chr19-48311595-G-A
• rs114554656
• NM_001364171.2:c.555C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-48311595-G-A
• chr19-48311595-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2 BP4_Strong BP6_Very_Strong BP7 BS1

The NM_001364171.2(ODAD1):​c.555C>T​(p.Ile185Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,551,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00060 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: ODAD1 NM_001364171.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.56

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 -15 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 19-48311595-G-A is Benign according to our data. Variant chr19-48311595-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 413796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.56 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000605 (92/152162) while in subpopulation AFR AF= 0.002 (83/41528). AF 95% confidence interval is 0.00165. There are 0 homozygotes in gnomad4. There are 47 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD1	NM_001364171.2	c.555C>T	p.Ile185Ile	synonymous_variant	Exon 7 of 16	ENST00000674294.1	NP_001351100.1
ODAD1	NM_144577.4	c.444C>T	p.Ile148Ile	synonymous_variant	Exon 5 of 14		NP_653178.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD1	ENST00000674294.1	c.555C>T	p.Ile185Ile	synonymous_variant	Exon 7 of 16		NM_001364171.2	ENSP00000501363.1

Frequencies

GnomAD3 genomes AF: 0.000612 AC: 93 AN: 152044 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00200

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000961

GnomAD3 exomes AF: 0.000173 AC: 27 AN: 156408 Hom.: 0 AF XY: 0.0000844 AC XY: 7 AN XY: 82918

Gnomad AFR exome AF: 0.00227

Gnomad AMR exome AF: 0.000122

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000917

Gnomad SAS exome AF: 0.0000878

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000496

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000102 AC: 143 AN: 1399030 Hom.: 0 Cov.: 30 AF XY: 0.0000898 AC XY: 62 AN XY: 690056

Gnomad4 AFR exome AF: 0.00260

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.0000406

Gnomad4 NFE exome AF: 0.0000426

Gnomad4 OTH exome AF: 0.000121

GnomAD4 genome AF: 0.000605 AC: 92 AN: 152162 Hom.: 0 Cov.: 31 AF XY: 0.000632 AC XY: 47 AN XY: 74390

Gnomad4 AFR AF: 0.00200

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000951

Alfa AF: 0.000344 Hom.: 0

Bravo AF: 0.000729

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:2

Dec 31, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 23, 2021

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

ODAD1-related disorder Benign:1

Apr 23, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.38
DANN	Benign	0.83

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: rs114554656; hg19: chr19-48814852;