19-48318562-C-T

Variant names:

• chr19-48318562-C-T
• rs7248372
• NM_001364171.2:c.185G>A

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.185G>A​(p.Arg62His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,551,252 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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. R62C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.016 (69 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (44 hom.)
• Consequence: ODAD1 NM_001364171.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.623
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017105937).
• BP6: Variant 19-48318562-C-T is Benign according to our data. Variant chr19-48318562-C-T is described in ClinVar as Benign. ClinVar VariationId is 262506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0522 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.185G>A	p.Arg62His	missense	Exon 5 of 16	NP_001351100.1
	ODAD1	NM_144577.4		c.74G>A	p.Arg25His	missense	Exon 3 of 14	NP_653178.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD1	ENST00000674294.1	MANE Select	c.185G>A	p.Arg62His	missense	Exon 5 of 16	ENSP00000501363.1
	ODAD1	ENST00000315396.7	TSL:1	c.74G>A	p.Arg25His	missense	Exon 3 of 14	ENSP00000318429.7
	ODAD1	ENST00000474199.6	TSL:2	c.185G>A	p.Arg62His	missense	Exon 5 of 15	ENSP00000501357.1

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2349 AN: 152088 Hom.: 68 Cov.: 31

Gnomad AFR AF: 0.0539

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00596

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00908

GnomAD2 exomes AF: 0.00372 AC: 573 AN: 153962 AF XY: 0.00295

Gnomad AFR exome AF: 0.0603

Gnomad AMR exome AF: 0.00284

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.00208

GnomAD4 exome AF: 0.00162 AC: 2271 AN: 1399046 Hom.: 44 Cov.: 31 AF XY: 0.00146 AC XY: 1008 AN XY: 690000

African (AFR) AF: 0.0599 AC: 1893 AN: 31594

American (AMR) AF: 0.00319 AC: 114 AN: 35694

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 35728

South Asian (SAS) AF: 0.000177 AC: 14 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49154

Middle Eastern (MID) AF: 0.00334 AC: 19 AN: 5696

European-Non Finnish (NFE) AF: 0.0000547 AC: 59 AN: 1078788

Other (OTH) AF: 0.00297 AC: 172 AN: 57988

GnomAD4 genome AF: 0.0155 AC: 2361 AN: 152206 Hom.: 69 Cov.: 31 AF XY: 0.0155 AC XY: 1150 AN XY: 74412

African (AFR) AF: 0.0540 AC: 2242 AN: 41494

American (AMR) AF: 0.00595 AC: 91 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68016

Other (OTH) AF: 0.00899 AC: 19 AN: 2114

Alfa AF: 0.00556 Hom.: 44

Bravo AF: 0.0174

ESP6500AA AF: 0.0520 AC: 72

ESP6500EA AF: 0.000314 AC: 1

ExAC AF: 0.00547 AC: 150

Asia WGS AF: 0.00260 AC: 9 AN: 3478

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)
-	-	1	Primary ciliary dyskinesia 20 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.8
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0064	N
LIST_S2	Benign	0.62	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.41	N
PhyloP100		-0.62
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.020
Sift	Benign	0.21	T
Sift4G	Uncertain	0.048	D
Polyphen		0.26	B
Vest4		0.042
MVP		0.067
MPC		0.26
ClinPred		0.0025	T
GERP RS		-3.6
Varity_R		0.024
gMVP		0.30
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7248372; hg19: chr19-48821819;