1-86358801-T-G

Position:

• chr1-86358801-T-G

Variant summary

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

The NM_001366781.1(ODF2L):​c.1258A>C​(p.Lys420Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000641 in 1,248,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000064 (0 hom.)
• Consequence: ODF2L NM_001366781.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59

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]

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=0.13661751).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODF2L	NM_001366781.1	c.1258A>C	p.Lys420Gln	missense_variant	12/17	ENST00000460698.7	NP_001353710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODF2L	ENST00000460698.7	c.1258A>C	p.Lys420Gln	missense_variant	12/17	5	NM_001366781.1	ENSP00000433092.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000641 AC: 8 AN: 1248676 Hom.: 0 Cov.: 18 AF XY: 0.00000319 AC XY: 2 AN XY: 627068

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: 0.00000847

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

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

Sep 25, 2024

The c.1345A>C (p.K449Q) alteration is located in exon 13 (coding exon 12) of the ODF2L gene. This alteration results from a A to C substitution at nucleotide position 1345, causing the lysine (K) at amino acid position 449 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	Benign	0.092
BayesDel_addAF	Benign	0.00080	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T;T;.;.;T
Eigen	Benign	0.093
Eigen_PC	Benign	0.084
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.75	.;T;T;T;T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.5	M;.;.;.;M
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.8	N;N;N;N;N
REVEL	Benign	0.083
Sift	Benign	0.36	T;T;D;T;T
Sift4G	Benign	0.19	T;T;T;T;T
Polyphen		0.98	D;.;.;D;D
Vest4		0.39
MutPred		0.18		Loss of methylation at K449 (P = 0.0278);.;.;.;Loss of methylation at K449 (P = 0.0278);
MVP		0.50
MPC		0.060
ClinPred		0.77	D
GERP RS		3.1
Varity_R		0.086
gMVP		0.074

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

Other links and lift over

dbSNP: rs1658787099; hg19: chr1-86824484;