Variant 9-128460985-G-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_001351578.2(ODF2):c.416G>A(p.Arg139Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000719 in 1,614,004 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: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

ODF2
NM_001351578.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.33

Variant links:

Genes affected

ODF2 (HGNC:8114): (outer dense fiber of sperm tails 2) The outer dense fibers are cytoskeletal structures that surround the axoneme in the middle piece and principal piece of the sperm tail. The fibers function in maintaining the elastic structure and recoil of the sperm tail as well as in protecting the tail from shear forces during epididymal transport and ejaculation. Defects in the outer dense fibers lead to abnormal sperm morphology and infertility. This gene encodes one of the major outer dense fiber proteins. Alternative splicing results in multiple transcript variants. The longer transcripts, also known as 'Cenexins', encode proteins with a C-terminal extension that are differentially targeted to somatic centrioles and thought to be crucial for the formation of microtubule organizing centers. [provided by RefSeq, Oct 2010]

ODF2 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=0.102398306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODF2	NM_001351578.2 linkuse as main transcript	c.416G>A	p.Arg139Gln	missense_variant	4/21	ENST00000351030.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODF2	ENST00000351030.8 linkuse as main transcript	c.416G>A	p.Arg139Gln	missense_variant	4/21	2	NM_001351578.2	P3

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000119

AC:

AN:

251484

Hom.:

AF XY:

0.000191

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000849

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000732

AC:

107

AN:

1461834

Hom.:

Cov.:

AF XY:

0.0000976

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.000939

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ExAC

AF:

0.000148

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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 06, 2022

The c.416G>A (p.R139Q) alteration is located in exon 4 (coding exon 4) of the ODF2 gene. This alteration results from a G to A substitution at nucleotide position 416, causing the arginine (R) at amino acid position 139 to be replaced by a glutamine (Q). 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

Pathogenic

0.60

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.20

.;.;.;.;T;.;.;T;.;.;.;.;.;T;.;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.85

D;D;D;T;.;T;.;D;T;D;D;D;D;D;D;.

M_CAP

Benign

0.030

MetaRNN

Benign

0.10

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.30

MutationAssessor

Uncertain

2.0

.;M;.;.;M;.;.;M;M;.;.;.;M;.;.;.

MutationTaster

Benign

0.99

D;D;D;D;D;D;D;D;N

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.6

.;N;N;N;.;N;.;D;N;N;.;N;N;.;N;D

REVEL

Benign

0.15

Sift

Uncertain

0.0090

.;D;D;D;.;T;.;D;D;D;.;T;D;.;D;D

Sift4G

Pathogenic

0.0

D;D;T;D;T;T;T;T;D;D;D;T;D;D;T;T

Polyphen

0.61, 0.012, 0.36, 1.0, 0.20, 1.0

.;.;P;B;B;D;B;B;D;.;.;.;D;.;B;P

Vest4

0.50, 0.45, 0.50, 0.57, 0.32, 0.33, 0.49, 0.37, 0.38

MutPred

0.43

.;Loss of phosphorylation at S58 (P = 0.0961);.;.;Loss of phosphorylation at S58 (P = 0.0961);.;.;Loss of phosphorylation at S58 (P = 0.0961);Loss of phosphorylation at S58 (P = 0.0961);Loss of phosphorylation at S58 (P = 0.0961);Loss of phosphorylation at S58 (P = 0.0961);Loss of phosphorylation at S58 (P = 0.0961);Loss of phosphorylation at S58 (P = 0.0961);Loss of phosphorylation at S58 (P = 0.0961);.;.;

MVP

0.69

MPC

0.97

ClinPred

0.25

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.28

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

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