rs544728429
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_015214.3(DDHD2):āc.277T>Cā(p.Leu93=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000215 in 1,611,646 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: š 0.000085 ( 0 hom., cov: 32)
Exomes š: 0.00023 ( 0 hom. )
Consequence
DDHD2
NM_015214.3 synonymous
NM_015214.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.149
Genes affected
DDHD2 (HGNC:29106): (DDHD domain containing 2) This gene encodes a phospholipase enzyme containing sterile-alpha-motif (SAM), WWE, and DDHD domains. This protein participates in membrane trafficking between the endoplastic reticulum and the Golgi body. Mutations in this gene can cause autosomal recessive spastic paraplegia 54. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
Variant 8-38234450-T-C is Benign according to our data. Variant chr8-38234450-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 434904.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=-0.149 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DDHD2 | NM_015214.3 | c.277T>C | p.Leu93= | synonymous_variant | 3/18 | ENST00000397166.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DDHD2 | ENST00000397166.7 | c.277T>C | p.Leu93= | synonymous_variant | 3/18 | 2 | NM_015214.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000855 AC: 13AN: 152050Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000482 AC: 12AN: 249026Hom.: 0 AF XY: 0.0000594 AC XY: 8AN XY: 134730
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GnomAD4 exome AF: 0.000228 AC: 333AN: 1459596Hom.: 0 Cov.: 31 AF XY: 0.000229 AC XY: 166AN XY: 726158
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GnomAD4 genome ? AF: 0.0000855 AC: 13AN: 152050Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6AN XY: 74274
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 06, 2015 | - - |
Hereditary spastic paraplegia 54 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 19, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | DDHD2: BP4, BP7 - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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