1-86356523-T-G

Position:

• chr1-86356523-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001366781.1(ODF2L):​c.1352A>C​(p.His451Pro) 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 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ODF2L NM_001366781.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.594

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]

ODF2L (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05774343).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODF2L	NM_001366781.1	c.1352A>C	p.His451Pro	missense_variant	13/17	ENST00000460698.7	NP_001353710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODF2L	ENST00000460698.7	c.1352A>C	p.His451Pro	missense_variant	13/17	5	NM_001366781.1	ENSP00000433092.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461802 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727210

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

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

Jan 03, 2024

The c.1439A>C (p.H480P) alteration is located in exon 14 (coding exon 13) of the ODF2L gene. This alteration results from a A to C substitution at nucleotide position 1439, causing the histidine (H) at amino acid position 480 to be replaced by a proline (P). 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	0.24
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	14
DANN	Benign	0.58
DEOGEN2	Benign	0.023	T;T;.;T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.60	.;T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.058	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.;.;L
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Benign	0.22
Sift	Benign	0.13	T;T;T;T
Sift4G	Benign	0.12	T;T;T;T
Polyphen		0.63	P;.;P;P
Vest4		0.33
MutPred		0.10		Gain of glycosylation at H480 (P = 0.1918);.;.;Gain of glycosylation at H480 (P = 0.1918);
MVP		0.44
MPC		0.016
ClinPred		0.11	T
GERP RS		-0.43
Varity_R		0.16
gMVP		0.39

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: chr1-86822206;