chr19-48302758-C-T

Variant names:

• chr19-48302758-C-T
• rs34540645
• NM_001364171.2:c.1176G>A

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.1176G>A​(p.Ser392Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 1,613,612 control chromosomes in the GnomAD database, including 6,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (386 hom., cov: 32)
  • Exomes 𝑓: 0.082 (5633 hom.)
• Consequence: ODAD1 NM_001364171.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.35
• Publications: 6 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: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• 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=-0.78).
• BP6: Variant 19-48302758-C-T is Benign according to our data. Variant chr19-48302758-C-T is described in ClinVar as Benign. ClinVar VariationId is 262483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.35 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0909 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD1	NM_001364171.2	MANE Select	c.1176G>A	p.Ser392Ser	synonymous	Exon 12 of 16	NP_001351100.1	A0A6I8PTZ2
	ODAD1	NM_144577.4		c.1065G>A	p.Ser355Ser	synonymous	Exon 10 of 14	NP_653178.3	Q96M63-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD1	ENST00000674294.1	MANE Select	c.1176G>A	p.Ser392Ser	synonymous	Exon 12 of 16	ENSP00000501363.1	A0A6I8PTZ2
	ODAD1	ENST00000315396.7	TSL:1	c.1065G>A	p.Ser355Ser	synonymous	Exon 10 of 14	ENSP00000318429.7	Q96M63-1
	ODAD1	ENST00000859784.1		c.1236G>A	p.Ser412Ser	synonymous	Exon 11 of 15	ENSP00000529843.1

Frequencies

GnomAD3 genomes AF: 0.0601 AC: 9146 AN: 152202 Hom.: 386 Cov.: 32

Gnomad AFR AF: 0.0169

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0669

Gnomad ASJ AF: 0.0905

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0221

Gnomad FIN AF: 0.0392

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0929

Gnomad OTH AF: 0.0765

GnomAD2 exomes AF: 0.0604 AC: 15094 AN: 249964 AF XY: 0.0609

Gnomad AFR exome AF: 0.0144

Gnomad AMR exome AF: 0.0472

Gnomad ASJ exome AF: 0.0940

Gnomad EAS exome AF: 0.000327

Gnomad FIN exome AF: 0.0399

Gnomad NFE exome AF: 0.0909

Gnomad OTH exome AF: 0.0734

GnomAD4 exome AF: 0.0823 AC: 120296 AN: 1461292 Hom.: 5633 Cov.: 34 AF XY: 0.0805 AC XY: 58551 AN XY: 726974

African (AFR) AF: 0.0122 AC: 410 AN: 33480

American (AMR) AF: 0.0502 AC: 2245 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0946 AC: 2472 AN: 26132

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39700

South Asian (SAS) AF: 0.0242 AC: 2091 AN: 86256

European-Finnish (FIN) AF: 0.0412 AC: 2179 AN: 52906

Middle Eastern (MID) AF: 0.0501 AC: 289 AN: 5768

European-Non Finnish (NFE) AF: 0.0950 AC: 105607 AN: 1111948

Other (OTH) AF: 0.0827 AC: 4996 AN: 60382

GnomAD4 genome AF: 0.0600 AC: 9143 AN: 152320 Hom.: 386 Cov.: 32 AF XY: 0.0573 AC XY: 4269 AN XY: 74472

African (AFR) AF: 0.0168 AC: 699 AN: 41578

American (AMR) AF: 0.0668 AC: 1021 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0905 AC: 314 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0223 AC: 108 AN: 4834

European-Finnish (FIN) AF: 0.0392 AC: 416 AN: 10622

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0929 AC: 6316 AN: 68022

Other (OTH) AF: 0.0757 AC: 160 AN: 2114

Alfa AF: 0.0791 Hom.: 397

Bravo AF: 0.0603

Asia WGS AF: 0.0120 AC: 41 AN: 3478

EpiCase AF: 0.0966

EpiControl AF: 0.0963

ClinVar

ClinVar submissions

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	-0.78
CADD	Benign	0.12
DANN	Benign	0.57
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34540645; hg19: chr19-48806015; COSMIC: COSV59559007; COSMIC: COSV59559007;