1-86360466-T-C

Position:

• chr1-86360466-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04

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]

ACMG classification

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
ODF2L	NM_001366781.1	c.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
ODF2L	ENST00000460698.7	c.1127A>G	p.Glu376Gly	missense_variant	11/17	5	NM_001366781.1	ENSP00000433092.2

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

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2023

The 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

Other links and lift over

dbSNP: rs773676205; hg19: chr1-86826149;