9-128469311-G-T

Position:

• chr9-128469311-G-T

Variant summary

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

The NM_001351578.2(ODF2):​c.627G>T​(p.Lys209Asn) 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: 30)
• Consequence: ODF2 NM_001351578.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODF2	NM_001351578.2	c.627G>T	p.Lys209Asn	missense_variant	5/21	ENST00000351030.8
ODF2-AS1	NR_170291.1	n.81-28C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODF2	ENST00000351030.8	c.627G>T	p.Lys209Asn	missense_variant	5/21	2	NM_001351578.2	P3
ODF2-AS1	ENST00000420801.1	n.81-28C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

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

Jan 27, 2022

The c.570G>T (p.K190N) alteration is located in exon 5 (coding exon 5) of the ODF2 gene. This alteration results from a G to T substitution at nucleotide position 570, causing the lysine (K) at amino acid position 190 to be replaced by an asparagine (N). 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	0.77
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	.;.;.;.;T;.;T;.;.;.;.;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.97	D;D;D;D;.;.;D;D;D;D;D;.
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.30	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Uncertain	2.1	.;M;.;.;M;.;M;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.4	.;N;N;N;.;.;D;N;D;N;D;.
REVEL	Benign	0.18
Sift	Pathogenic	0.0	.;D;D;D;.;.;D;D;D;D;D;.
Sift4G	Uncertain	0.0080	D;D;T;D;T;T;T;D;D;D;T;T
Polyphen		1.0	.;.;D;.;D;D;D;D;.;D;D;D
Vest4		0.70, 0.70, 0.72, 0.69, 0.70, 0.70, 0.71, 0.69
MutPred		0.18		.;Loss of ubiquitination at K126 (P = 0.0326);.;.;Loss of ubiquitination at K126 (P = 0.0326);.;Loss of ubiquitination at K126 (P = 0.0326);.;.;.;.;.;
MVP		0.81
MPC		1.4
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.45
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.35		Position offset: 42

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: chr9-131231590; COSMIC: COSV100654379; COSMIC: COSV100654379;