rs144016130
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001160148.2(DDHD1):c.2408A>T(p.His803Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001160148.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DDHD1 | NM_001160148.2 | c.2408A>T | p.His803Leu | missense_variant | 11/13 | ENST00000673822.2 | NP_001153620.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DDHD1 | ENST00000673822.2 | c.2408A>T | p.His803Leu | missense_variant | 11/13 | NM_001160148.2 | ENSP00000500986 | A2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251324Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135824
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461704Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4AN XY: 727132
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74354
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 19, 2022 | The c.2408A>T (p.H803L) alteration is located in exon 11 (coding exon 11) of the DDHD1 gene. This alteration results from a A to T substitution at nucleotide position 2408, causing the histidine (H) at amino acid position 803 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Hereditary spastic paraplegia 28 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 09, 2022 | This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 810 of the DDHD1 protein (p.His810Leu). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with DDHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1307281). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 25, 2019 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; In addition, in-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at