Variant chr1-86358880-C-A 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.1179G>T(p.Leu393Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000294 in 1,360,070 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

ODF2L
NM_001366781.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0810

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:

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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=0.2632646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODF2L	NM_001366781.1 link	c.1179G>T	p.Leu393Phe	missense_variant	12/17	ENST00000460698.7	NP_001353710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODF2L	ENST00000460698.7 link	c.1179G>T	p.Leu393Phe	missense_variant	12/17	5	NM_001366781.1	ENSP00000433092.2		Q9ULJ1-4H0YD68

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000149

AC:

AN:

201106

Hom.:

AF XY:

0.0000274

AC XY:

AN XY:

109614

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:

0.0000324

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000294

AC:

AN:

1360070

Hom.:

Cov.:

AF XY:

0.00000444

AC XY:

AN XY:

676394

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000381

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

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

Feb 10, 2023

The c.1266G>T (p.L422F) alteration is located in exon 13 (coding exon 12) of the ODF2L gene. This alteration results from a G to T substitution at nucleotide position 1266, causing the leucine (L) at amino acid position 422 to be replaced by a phenylalanine (F). 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

0.22

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

T;T;.;.;T;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.86

.;D;T;D;T;D

M_CAP

Uncertain

0.093

MetaRNN

Benign

0.26

T;T;T;T;T;T

MetaSVM

Uncertain

-0.19

MutationAssessor

Uncertain

2.6

M;.;.;.;M;.

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.5

N;N;D;N;D;N

REVEL

Benign

0.19

Sift

Uncertain

0.0070

D;D;D;D;D;D

Sift4G

Benign

0.069

T;T;T;T;T;.

Polyphen

1.0

D;.;.;D;D;.

Vest4

0.41

MutPred

0.19

Gain of methylation at K421 (P = 0.0299);.;.;.;Gain of methylation at K421 (P = 0.0299);.;

MVP

0.75

MPC

0.068

ClinPred

0.82

GERP RS

3.5

Varity_R

0.13

gMVP

0.091

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

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