1-86360466-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001366781.1(ODF2L):​c.1127A>G​(p.Glu376Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ODF2L
NM_001366781.1 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04
Variant links:
Genes affected
ODF2L (HGNC:29225): (outer dense fiber of sperm tails 2 like) Involved in negative regulation of cilium assembly. Located in centriolar satellite and ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28105196).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ODF2LNM_001366781.1 linkc.1127A>G p.Glu376Gly missense_variant 11/17 ENST00000460698.7 NP_001353710.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ODF2LENST00000460698.7 linkc.1127A>G p.Glu376Gly missense_variant 11/175 NM_001366781.1 ENSP00000433092.2 Q9ULJ1-4H0YD68

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000403
AC:
1
AN:
248446
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134360
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000886
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
26
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 12, 2023The c.1214A>G (p.E405G) alteration is located in exon 12 (coding exon 11) of the ODF2L gene. This alteration results from a A to G substitution at nucleotide position 1214, causing the glutamic acid (E) at amino acid position 405 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.080
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T;T;.;.;T;T
Eigen
Uncertain
0.28
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.83
.;T;T;T;T;D
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.28
T;T;T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Uncertain
2.5
M;.;.;.;M;.
PrimateAI
Benign
0.42
T
PROVEAN
Uncertain
-3.5
D;D;D;D;D;D
REVEL
Benign
0.22
Sift
Benign
0.065
T;T;T;T;T;T
Sift4G
Pathogenic
0.0
D;D;D;D;D;.
Polyphen
1.0
D;.;.;D;D;.
Vest4
0.51
MutPred
0.21
Loss of ubiquitination at K407 (P = 0.0391);.;.;.;Loss of ubiquitination at K407 (P = 0.0391);.;
MVP
0.79
MPC
0.068
ClinPred
0.94
D
GERP RS
5.9
Varity_R
0.10
gMVP
0.13

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs773676205; hg19: chr1-86826149; API