chr9-128472947-T-C

Position:

• chr9-128472947-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001351578.2(ODF2):​c.865T>C​(p.Cys289Arg) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ODF2 NM_001351578.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.63

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-AS1 (HGNC:):

ACMG classification

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=0.1351574).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODF2	NM_001351578.2	c.865T>C	p.Cys289Arg	missense_variant	7/21	ENST00000351030.8	NP_001338507.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODF2	ENST00000351030.8	c.865T>C	p.Cys289Arg	missense_variant	7/21	2	NM_001351578.2	ENSP00000342581.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Aug 21, 2023

The c.808T>C (p.C270R) alteration is located in exon 7 (coding exon 7) of the ODF2 gene. This alteration results from a T to C substitution at nucleotide position 808, causing the cysteine (C) at amino acid position 270 to be replaced by an arginine (R). 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	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Benign	0.87
DEOGEN2	Benign	0.26	.;.;.;T;.;.;T;.;.;.;.;.;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.053
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.63	T;T;T;.;T;.;T;T;T;T;T;T;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.14	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.92	L;.;.;L;.;.;L;.;.;.;.;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-2.4	N;N;N;.;N;.;.;N;.;D;N;D;.
REVEL	Benign	0.050
Sift	Benign	0.065	T;D;T;.;D;.;.;T;.;T;T;T;.
Sift4G	Benign	0.48	T;T;T;T;T;T;T;T;T;D;T;T;T
Polyphen		0.51, 0.68, 0.27, 0.19	.;P;P;P;B;B;P;B;.;.;B;B;P
Vest4		0.49
MutPred		0.26		Gain of MoRF binding (P = 0.0021);.;.;Gain of MoRF binding (P = 0.0021);.;.;Gain of MoRF binding (P = 0.0021);.;.;.;.;.;.;
MVP		0.55
MPC		0.76
ClinPred		0.31	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.33
gMVP		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-131235226;