Variant 1-86360428-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001366781.1(ODF2L):c.1165C>G(p.Gln389Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000803 in 1,246,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

ODF2L
NM_001366781.1 missense, splice_region

Scores

Splicing: ADA: 0.0009803

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31

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]

ODF2L links:

ODF2L (HGNC:):

ODF2L links:

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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=0.23078024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODF2L	NM_001366781.1 linkuse as main transcript	c.1165C>G	p.Gln389Glu	missense_variant, splice_region_variant	11/17	ENST00000460698.7	NP_001353710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODF2L	ENST00000460698.7 linkuse as main transcript	c.1165C>G	p.Gln389Glu	missense_variant, splice_region_variant	11/17	5	NM_001366781.1	ENSP00000433092.2		Q9ULJ1-4H0YD68

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000433

AC:

AN:

231124

Hom.:

AF XY:

0.00

AC XY:

AN XY:

125186

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000347

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

8.03e-7

AC:

AN:

1246042

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

629804

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000257

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

May 30, 2024

The c.1252C>G (p.Q418E) alteration is located in exon 12 (coding exon 11) of the ODF2L gene. This alteration results from a C to G substitution at nucleotide position 1252, causing the glutamine (Q) at amino acid position 418 to be replaced by a glutamic acid (E). 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

0.065

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.23

T;T;.;.;T;T

Eigen

Benign

0.020

Eigen_PC

Benign

0.038

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.74

.;T;T;T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.23

T;T;T;T;T;T

MetaSVM

Uncertain

-0.18

MutationAssessor

Uncertain

2.2

M;.;.;.;M;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.2

N;N;N;N;N;N

REVEL

Benign

0.23

Sift

Benign

0.14

T;T;T;T;T;T

Sift4G

Benign

0.30

T;T;T;T;T;.

Polyphen

1.0

D;.;.;D;D;.

Vest4

0.30

MutPred

0.19

Loss of MoRF binding (P = 0.0313);.;.;.;Loss of MoRF binding (P = 0.0313);.;

MVP

0.55

MPC

0.011

ClinPred

0.14

GERP RS

5.0

Varity_R

0.23

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00098

dbscSNV1_RF

Benign

0.19

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

Publications

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over