19-48297143-C-A

Variant names:

• chr19-48297143-C-A
• rs780679601
• NM_001364171.2:c.1957G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001364171.2(ODAD1):​c.1957G>T​(p.Val653Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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. V653M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ODAD1 NM_001364171.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.01
• 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: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.023873687).

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.1957G>T	p.Val653Leu	missense	Exon 16 of 16	NP_001351100.1
	ODAD1	NM_144577.4		c.1846G>T	p.Val616Leu	missense	Exon 14 of 14	NP_653178.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD1	ENST00000674294.1	MANE Select	c.1957G>T	p.Val653Leu	missense	Exon 16 of 16	ENSP00000501363.1
	ODAD1	ENST00000315396.7	TSL:1	c.1846G>T	p.Val616Leu	missense	Exon 14 of 14	ENSP00000318429.7
	ODAD1	ENST00000497273.1	TSL:2	n.1392G>T		non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.0010
DANN	Benign	0.65
DEOGEN2	Benign	0.00070	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.26	N
PhyloP100		-6.0
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.0040
Sift	Benign	0.60	T
Sift4G	Benign	0.67	T
Polyphen		0.0010	B
Vest4		0.042
MutPred		0.075		Gain of relative solvent accessibility (P = 0.1571)
MVP		0.085
MPC		0.20
ClinPred		0.038	T
GERP RS		-8.8
Varity_R		0.030
gMVP		0.062
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: rs780679601; hg19: chr19-48800400;