rs138906273
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1
The NM_001160148.2(DDHD1):c.1524A>G(p.Gln508=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,613,696 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0019 ( 8 hom. )
Consequence
DDHD1
NM_001160148.2 synonymous
NM_001160148.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.74
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 14-53063185-T-C is Benign according to our data. Variant chr14-53063185-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 380535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-53063185-T-C is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1.74 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00148 (225/152330) while in subpopulation NFE AF= 0.00248 (169/68028). AF 95% confidence interval is 0.00218. There are 1 homozygotes in gnomad4. There are 106 alleles in male gnomad4 subpopulation. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DDHD1 | NM_001160148.2 | c.1524A>G | p.Gln508= | synonymous_variant | 7/13 | ENST00000673822.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DDHD1 | ENST00000673822.2 | c.1524A>G | p.Gln508= | synonymous_variant | 7/13 | NM_001160148.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00148 AC: 225AN: 152212Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00151 AC: 379AN: 250882Hom.: 1 AF XY: 0.00162 AC XY: 220AN XY: 135624
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GnomAD4 exome AF: 0.00185 AC: 2705AN: 1461366Hom.: 8 Cov.: 34 AF XY: 0.00180 AC XY: 1305AN XY: 726998
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 18, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | DDHD1: BP4, BP7 - |
Hereditary spastic paraplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Mar 30, 2021 | - - |
Hereditary spastic paraplegia 28 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 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