rs114078313

Variant names:

• chr19-48304076-C-T
• rs114078313
• NM_001364171.2:c.730G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001364171.2(ODAD1):​c.730G>A​(p.Glu244Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000753 in 1,614,100 control chromosomes in the GnomAD database, including 9 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00040 (5 hom.)
• Consequence: ODAD1 NM_001364171.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.219
• Publications: 2 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=0.0044665635).
• BP6: Variant 19-48304076-C-T is Benign according to our data. Variant chr19-48304076-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 241879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00415 (633/152352) while in subpopulation AFR AF = 0.0145 (604/41594). AF 95% confidence interval is 0.0136. There are 4 homozygotes in GnomAd4. There are 323 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR,AD gene

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.730G>A	p.Glu244Lys	missense	Exon 9 of 16	NP_001351100.1	A0A6I8PTZ2
	ODAD1	NM_144577.4		c.619G>A	p.Glu207Lys	missense	Exon 7 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.730G>A	p.Glu244Lys	missense	Exon 9 of 16	ENSP00000501363.1	A0A6I8PTZ2
	ODAD1	ENST00000315396.7	TSL:1	c.619G>A	p.Glu207Lys	missense	Exon 7 of 14	ENSP00000318429.7	Q96M63-1
	ODAD1	ENST00000859784.1		c.730G>A	p.Glu244Lys	missense	Exon 8 of 15	ENSP00000529843.1

Frequencies

GnomAD3 genomes AF: 0.00415 AC: 632 AN: 152234 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00108 AC: 271 AN: 251296 AF XY: 0.000766

Gnomad AFR exome AF: 0.0146

Gnomad AMR exome AF: 0.000810

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000399 AC: 583 AN: 1461748 Hom.: 5 Cov.: 34 AF XY: 0.000323 AC XY: 235 AN XY: 727180

African (AFR) AF: 0.0142 AC: 477 AN: 33480

American (AMR) AF: 0.000917 AC: 41 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111940

Other (OTH) AF: 0.000927 AC: 56 AN: 60394

GnomAD4 genome AF: 0.00415 AC: 633 AN: 152352 Hom.: 4 Cov.: 33 AF XY: 0.00434 AC XY: 323 AN XY: 74502

African (AFR) AF: 0.0145 AC: 604 AN: 41594

American (AMR) AF: 0.00124 AC: 19 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68034

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00152 Hom.: 1

Bravo AF: 0.00456

ESP6500AA AF: 0.0145 AC: 64

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00124 AC: 151

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely 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
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.22
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.064
Sift	Benign	0.28	T
Sift4G	Benign	0.10	T
Polyphen		0.95	P
Vest4		0.23
MVP		0.27
MPC		0.33
ClinPred		0.0033	T
GERP RS		-0.42
Varity_R		0.077
gMVP		0.23
Mutation Taster		=99/1	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: rs114078313; hg19: chr19-48807333;