chr19-48296995-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001364171.2(ODAD1):​c.2105G>C​(p.Ser702Thr) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ODAD1
NM_001364171.2 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.637
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13304344).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ODAD1NM_001364171.2 linkuse as main transcriptc.2105G>C p.Ser702Thr missense_variant 16/16 ENST00000674294.1
ODAD1NM_144577.4 linkuse as main transcriptc.1994G>C p.Ser665Thr missense_variant 14/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ODAD1ENST00000674294.1 linkuse as main transcriptc.2105G>C p.Ser702Thr missense_variant 16/16 NM_001364171.2 P2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeNov 18, 2023This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 665 of the CCDC114 protein (p.Ser665Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CCDC114-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0067
T
Eigen
Benign
-0.29
Eigen_PC
Benign
-0.35
FATHMM_MKL
Benign
0.34
N
LIST_S2
Benign
0.43
T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.043
Sift
Benign
0.040
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.71
P
Vest4
0.12
MutPred
0.13
Gain of glycosylation at S663 (P = 0.0921);
MVP
0.37
MPC
0.52
ClinPred
0.44
T
GERP RS
1.4
Varity_R
0.10
gMVP
0.16

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-48800252; API