chr19-48303720-G-A

Variant names:

• chr19-48303720-G-A
• rs2242463
• NM_001364171.2:c.918C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001364171.2(ODAD1):​c.918C>T​(p.Asp306Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,613,800 control chromosomes in the GnomAD database, including 29,201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2525 hom., cov: 32)
  • Exomes 𝑓: 0.19 (26676 hom.)
• Consequence: ODAD1 NM_001364171.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.86
• Publications: 16 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 19-48303720-G-A is Benign according to our data. Variant chr19-48303720-G-A is described in ClinVar as Benign. ClinVar VariationId is 262507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.86 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

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.918C>T	p.Asp306Asp	synonymous	Exon 10 of 16	NP_001351100.1
	ODAD1	NM_144577.4		c.807C>T	p.Asp269Asp	synonymous	Exon 8 of 14	NP_653178.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD1	ENST00000674294.1	MANE Select	c.918C>T	p.Asp306Asp	synonymous	Exon 10 of 16	ENSP00000501363.1
	ODAD1	ENST00000315396.7	TSL:1	c.807C>T	p.Asp269Asp	synonymous	Exon 8 of 14	ENSP00000318429.7
	ODAD1	ENST00000474199.6	TSL:2	c.918C>T	p.Asp306Asp	synonymous	Exon 10 of 15	ENSP00000501357.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27032 AN: 152040 Hom.: 2523 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.170

GnomAD2 exomes AF: 0.178 AC: 44651 AN: 251178 AF XY: 0.183

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.0838

Gnomad ASJ exome AF: 0.185

Gnomad EAS exome AF: 0.127

Gnomad FIN exome AF: 0.262

Gnomad NFE exome AF: 0.200

Gnomad OTH exome AF: 0.171

GnomAD4 exome AF: 0.187 AC: 273514 AN: 1461642 Hom.: 26676 Cov.: 34 AF XY: 0.188 AC XY: 136623 AN XY: 727150

African (AFR) AF: 0.153 AC: 5120 AN: 33476

American (AMR) AF: 0.0870 AC: 3887 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 4711 AN: 26120

East Asian (EAS) AF: 0.115 AC: 4564 AN: 39696

South Asian (SAS) AF: 0.177 AC: 15275 AN: 86246

European-Finnish (FIN) AF: 0.254 AC: 13547 AN: 53418

Middle Eastern (MID) AF: 0.183 AC: 1055 AN: 5766

European-Non Finnish (NFE) AF: 0.193 AC: 214749 AN: 1111836

Other (OTH) AF: 0.176 AC: 10606 AN: 60390

GnomAD4 genome AF: 0.178 AC: 27037 AN: 152158 Hom.: 2525 Cov.: 32 AF XY: 0.180 AC XY: 13387 AN XY: 74378

African (AFR) AF: 0.156 AC: 6491 AN: 41512

American (AMR) AF: 0.114 AC: 1744 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 614 AN: 3468

East Asian (EAS) AF: 0.124 AC: 641 AN: 5176

South Asian (SAS) AF: 0.177 AC: 852 AN: 4822

European-Finnish (FIN) AF: 0.260 AC: 2752 AN: 10594

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13401 AN: 67984

Other (OTH) AF: 0.170 AC: 359 AN: 2110

Alfa AF: 0.186 Hom.: 9372

Bravo AF: 0.167

Asia WGS AF: 0.150 AC: 523 AN: 3478

EpiCase AF: 0.189

EpiControl AF: 0.185

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.97
DANN	Benign	0.88
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs2242463; hg19: chr19-48806977; COSMIC: COSV59555635; COSMIC: COSV59555635;