chr19-48311595-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. 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
• Publications: 0 publications found

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]

ODAD1 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 20

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• 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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364171.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD1	ENST00000674294.1	MANE Select	c.555C>T	p.Ile185Ile	synonymous	Exon 7 of 16	ENSP00000501363.1
	ODAD1	ENST00000315396.7	TSL:1	c.444C>T	p.Ile148Ile	synonymous	Exon 5 of 14	ENSP00000318429.7
	ODAD1	ENST00000859784.1		c.555C>T	p.Ile185Ile	synonymous	Exon 6 of 15	ENSP00000529843.1

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

GnomAD2 exomes AF: 0.000173 AC: 27 AN: 156408 AF XY: 0.0000844

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 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

African (AFR) AF: 0.00260 AC: 82 AN: 31598

American (AMR) AF: 0.000112 AC: 4 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35726

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79220

European-Finnish (FIN) AF: 0.0000406 AC: 2 AN: 49254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.0000426 AC: 46 AN: 1078686

Other (OTH) AF: 0.000121 AC: 7 AN: 57982

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

African (AFR) AF: 0.00200 AC: 83 AN: 41528

American (AMR) AF: 0.000327 AC: 5 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68016

Other (OTH) AF: 0.000951 AC: 2 AN: 2104

Alfa AF: 0.000344 Hom.: 0

Bravo AF: 0.000729

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Primary ciliary dyskinesia (2)
-	-	1	ODAD1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.38
DANN	Benign	0.83
PhyloP100		-3.6
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs114554656; hg19: chr19-48814852;