rs367621941
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_001160148.2(DDHD1):c.156C>T(p.Gly52Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000977 in 1,596,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00076 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0010 ( 0 hom. )
Consequence
DDHD1
NM_001160148.2 synonymous
NM_001160148.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.52
Genes affected
DDHD1 (HGNC:19714): (DDHD domain containing 1) This gene is a member of the intracellular phospholipase A1 gene family. The protein encoded by this gene preferentially hydrolyzes phosphatidic acid. It is a cytosolic protein with some mitochondrial localization, and is thought to be involved in the regulation of mitochondrial dynamics. Overexpression of this gene causes fragmentation of the tubular structures in mitochondria, while depletion of the gene results in mitochondrial tubule elongation. Deletion of this gene in male mice caused fertility defects, resulting from disruption in the organization of the mitochondria during spermiogenesis. In humans, mutations in this gene have been associated with hereditary spastic paraplegia (HSP), also known as Strumpell-Lorrain disease, or, familial spastic paraparesis (FSP). This inherited disorder is characterized by progressive weakness and spasticity of the legs. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 14-53152943-G-A is Benign according to our data. Variant chr14-53152943-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 415256.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=1.52 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000757 (115/151956) while in subpopulation AMR AF= 0.00222 (34/15292). AF 95% confidence interval is 0.00164. There are 0 homozygotes in gnomad4. There are 61 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| DDHD1 | NM_001160148.2 | c.156C>T | p.Gly52Gly | synonymous_variant | 1/13 | ENST00000673822.2 | NP_001153620.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| DDHD1 | ENST00000673822.2 | c.156C>T | p.Gly52Gly | synonymous_variant | 1/13 | NM_001160148.2 | ENSP00000500986.2 | |||
| DDHD1 | ENST00000357758.3 | c.156C>T | p.Gly52Gly | synonymous_variant | 1/12 | 1 | ENSP00000350401.3 | |||
| DDHD1 | ENST00000395606.5 | c.156C>T | p.Gly52Gly | synonymous_variant | 1/13 | 2 | ENSP00000378970.1 |
Frequencies
GnomAD3 genomes 0.000757 AC: 115AN: 151840Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000629 AC: 131AN: 208346Hom.: 0 AF XY: 0.000697 AC XY: 80AN XY: 114702
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GnomAD4 exome AF: 0.00100 AC: 1445AN: 1444696Hom.: 0 Cov.: 35 AF XY: 0.000986 AC XY: 708AN XY: 717690
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GnomAD4 genome 0.000757 AC: 115AN: 151956Hom.: 0 Cov.: 32 AF XY: 0.000821 AC XY: 61AN XY: 74286
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:2
| Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 20, 2020 | - - |
| Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2024 | DDHD1: BP4, BP7 - |
Hereditary spastic paraplegia Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Dec 28, 2016 | - - |
Hereditary spastic paraplegia 28 Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 27, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at