NM_001364171.2:c.1514C>G

Variant names:

• chr19-48297657-G-C
• rs35461177
• NM_001364171.2:c.1514C>G
• ODAD1 p.Pro505Arg

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001364171.2(ODAD1):​c.1514C>G​(p.Pro505Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000736 in 1,358,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P505L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: ODAD1 NM_001364171.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.798
• Publications: 0 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: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24427876).

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.1514C>G	p.Pro505Arg	missense	Exon 15 of 16	NP_001351100.1	A0A6I8PTZ2
	ODAD1	NM_144577.4		c.1403C>G	p.Pro468Arg	missense	Exon 13 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.1514C>G	p.Pro505Arg	missense	Exon 15 of 16	ENSP00000501363.1	A0A6I8PTZ2
	ODAD1	ENST00000315396.7	TSL:1	c.1403C>G	p.Pro468Arg	missense	Exon 13 of 14	ENSP00000318429.7	Q96M63-1
	ODAD1	ENST00000859784.1		c.1574C>G	p.Pro525Arg	missense	Exon 14 of 15	ENSP00000529843.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.36e-7 AC: 1 AN: 1358350 Hom.: 0 Cov.: 35 AF XY: 0.00000150 AC XY: 1 AN XY: 664942

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30018

American (AMR) AF: 0.00 AC: 0 AN: 27618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19638

East Asian (EAS) AF: 0.00 AC: 0 AN: 38596

South Asian (SAS) AF: 0.0000144 AC: 1 AN: 69586

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1062398

Other (OTH) AF: 0.00 AC: 0 AN: 55770

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.0010
Eigen_PC	Benign	-0.065
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.80
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.038
Sift	Benign	0.17	T
Sift4G	Uncertain	0.0080	D
Varity_R		0.075
gMVP		0.041
Mutation Taster		=90/10	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs35461177;

hg19: chr19-48800914;