chr9-128472947-T-G

Variant names:

• chr9-128472947-T-G
• rs2131794010
• NM_001351578.2:c.865T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001351578.2(ODF2):​c.865T>G​(p.Cys289Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C289R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ODF2 NM_001351578.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.63
• Publications: 0 publications found

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:49461): (ODF2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15807399).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODF2	NM_001351578.2	c.865T>G	p.Cys289Gly	missense_variant	Exon 7 of 21	ENST00000351030.8	NP_001338507.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODF2	ENST00000351030.8	c.865T>G	p.Cys289Gly	missense_variant	Exon 7 of 21	2	NM_001351578.2	ENSP00000342581.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461810 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727212

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111974

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Benign	0.93
DEOGEN2	Uncertain	0.57	.;.;.;D;.;.;D;.;.;.;.;.;.
Eigen	Benign	-0.087
Eigen_PC	Benign	-0.029
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.93	D;D;D;.;D;.;D;D;D;D;D;D;.
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.16	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.6	L;.;.;L;.;.;L;.;.;.;.;.;.
PhyloP100		2.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.1	D;N;N;.;D;.;.;D;.;D;D;D;.
REVEL	Benign	0.14
Sift	Benign	0.052	T;D;T;.;D;.;.;D;.;D;D;D;.
Sift4G	Benign	0.40	T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.85, 0.67, 0.56	.;P;P;P;P;P;P;P;.;.;P;P;P
Vest4		0.72
MutPred		0.23		Loss of stability (P = 0.014);.;.;Loss of stability (P = 0.014);.;.;Loss of stability (P = 0.014);.;.;.;.;.;.;
MVP		0.58
MPC		0.73
ClinPred		0.56	D
GERP RS		3.3
Varity_R		0.16
gMVP		0.13
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs2131794010; hg19: chr9-131235226;