rs61747754

Variant names:

• chr19-48297494-C-A
• rs61747754
• NM_001364171.2:c.1606G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001364171.2(ODAD1):​c.1606G>T​(p.Ala536Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,602,864 control chromosomes in the GnomAD database, including 22,199 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A536V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.14 (1762 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20437 hom.)
• Consequence: ODAD1 NM_001364171.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.193
• Publications: 14 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024385154).
• BP6: Variant 19-48297494-C-A is Benign according to our data. Variant chr19-48297494-C-A is described in ClinVar as Benign. ClinVar VariationId is 262491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 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.1606G>T	p.Ala536Ser	missense	Exon 16 of 16	NP_001351100.1	A0A6I8PTZ2
	ODAD1	NM_144577.4		c.1495G>T	p.Ala499Ser	missense	Exon 14 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.1606G>T	p.Ala536Ser	missense	Exon 16 of 16	ENSP00000501363.1	A0A6I8PTZ2
	ODAD1	ENST00000315396.7	TSL:1	c.1495G>T	p.Ala499Ser	missense	Exon 14 of 14	ENSP00000318429.7	Q96M63-1
	ODAD1	ENST00000859784.1		c.1666G>T	p.Ala556Ser	missense	Exon 15 of 15	ENSP00000529843.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21824 AN: 151942 Hom.: 1764 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0986

Gnomad FIN AF: 0.0727

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.158

GnomAD2 exomes AF: 0.128 AC: 29332 AN: 229090 AF XY: 0.131

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.0829

Gnomad ASJ exome AF: 0.252

Gnomad EAS exome AF: 0.000228

Gnomad FIN exome AF: 0.0715

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.155

GnomAD4 exome AF: 0.161 AC: 234267 AN: 1450804 Hom.: 20437 Cov.: 63 AF XY: 0.160 AC XY: 115309 AN XY: 721414

African (AFR) AF: 0.137 AC: 4566 AN: 33288

American (AMR) AF: 0.0900 AC: 3924 AN: 43596

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 6652 AN: 25610

East Asian (EAS) AF: 0.000278 AC: 11 AN: 39504

South Asian (SAS) AF: 0.112 AC: 9533 AN: 85382

European-Finnish (FIN) AF: 0.0770 AC: 3825 AN: 49702

Middle Eastern (MID) AF: 0.196 AC: 1111 AN: 5680

European-Non Finnish (NFE) AF: 0.176 AC: 194732 AN: 1108142

Other (OTH) AF: 0.165 AC: 9913 AN: 59900

GnomAD4 genome AF: 0.144 AC: 21830 AN: 152060 Hom.: 1762 Cov.: 32 AF XY: 0.136 AC XY: 10104 AN XY: 74342

African (AFR) AF: 0.135 AC: 5617 AN: 41474

American (AMR) AF: 0.129 AC: 1975 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 913 AN: 3472

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5174

South Asian (SAS) AF: 0.0985 AC: 474 AN: 4814

European-Finnish (FIN) AF: 0.0727 AC: 771 AN: 10598

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11599 AN: 67938

Other (OTH) AF: 0.157 AC: 330 AN: 2108

Alfa AF: 0.155 Hom.: 3327

Bravo AF: 0.148

TwinsUK AF: 0.182 AC: 674

ALSPAC AF: 0.181 AC: 696

ESP6500AA AF: 0.138 AC: 607

ESP6500EA AF: 0.169 AC: 1445

ExAC AF: 0.123 AC: 14837

Asia WGS AF: 0.0460 AC: 162 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.1
DANN	Benign	0.57
DEOGEN2	Benign	0.00079	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.19
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.18	N
REVEL	Benign	0.060
Sift	Benign	0.55	T
Sift4G	Benign	1.0	T
Polyphen		0.091	B
Vest4		0.041
MPC		0.21
ClinPred		0.0013	T
GERP RS		0.55
Varity_R		0.038
gMVP		0.061
Mutation Taster		=99/1	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: rs61747754; hg19: chr19-48800751; COSMIC: COSV106458623;