Variant 1-86354531-T-G 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.1679A>C(p.Lys560Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,432,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ODF2L
NM_001366781.1 missense, splice_region

Scores

Splicing: ADA: 0.8901

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71

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=0.1876615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODF2L	NM_001366781.1 link	c.1679A>C	p.Lys560Thr	missense_variant, splice_region_variant	15/17	ENST00000460698.7	NP_001353710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODF2L	ENST00000460698.7 link	c.1679A>C	p.Lys560Thr	missense_variant, splice_region_variant	15/17	5	NM_001366781.1	ENSP00000433092.2		Q9ULJ1-4H0YD68

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1432736

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

712798

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:

0.00000182

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 07, 2024

The c.1766A>C (p.K589T) alteration is located in exon 16 (coding exon 15) of the ODF2L gene. This alteration results from a A to C substitution at nucleotide position 1766, causing the lysine (K) at amino acid position 589 to be replaced by a threonine (T). 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

0.24

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

T;T;.;T;.;T

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

.;D;T;D;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.19

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.1

M;.;.;.;.;M

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.6

D;D;D;D;D;N

REVEL

Benign

0.057

Sift

Uncertain

0.017

D;T;T;T;T;T

Sift4G

Uncertain

0.0060

D;D;D;.;D;D

Polyphen

1.0

D;.;.;.;D;D

Vest4

0.15

MutPred

0.18

Loss of ubiquitination at K589 (P = 0.0017);.;.;.;.;Loss of ubiquitination at K589 (P = 0.0017);

MVP

0.49

MPC

0.061

ClinPred

0.91

GERP RS

6.0

Varity_R

0.12

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.89

dbscSNV1_RF

Pathogenic

0.77

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over