chr8-38233190-C-T
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_015214.3(DDHD2):c.196C>T(p.Gln66*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
DDHD2
NM_015214.3 stop_gained
NM_015214.3 stop_gained
Scores
3
2
1
Clinical Significance
Conservation
PhyloP100: 1.14
Publications
0 publications found
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]
DDHD2 Gene-Disease associations (from GenCC):
- hereditary spastic paraplegia 54Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 8-38233190-C-T is Pathogenic according to our data. Variant chr8-38233190-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 2067256.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_015214.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DDHD2 | NM_015214.3 | MANE Select | c.196C>T | p.Gln66* | stop_gained | Exon 2 of 18 | NP_056029.2 | O94830-1 | |
| DDHD2 | NM_001164232.2 | c.196C>T | p.Gln66* | stop_gained | Exon 2 of 18 | NP_001157704.1 | O94830-1 | ||
| DDHD2 | NM_001362911.2 | c.196C>T | p.Gln66* | stop_gained | Exon 2 of 18 | NP_001349840.1 | O94830-1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DDHD2 | ENST00000397166.7 | TSL:2 MANE Select | c.196C>T | p.Gln66* | stop_gained | Exon 2 of 18 | ENSP00000380352.2 | O94830-1 | |
| DDHD2 | ENST00000853787.1 | c.196C>T | p.Gln66* | stop_gained | Exon 2 of 18 | ENSP00000523846.1 | |||
| DDHD2 | ENST00000520272.6 | TSL:2 | c.196C>T | p.Gln66* | stop_gained | Exon 2 of 18 | ENSP00000429932.2 | O94830-1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461612Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727126 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461612
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727126
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33472
American (AMR)
AF:
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26126
East Asian (EAS)
AF:
AC:
0
AN:
39696
South Asian (SAS)
AF:
AC:
0
AN:
86248
European-Finnish (FIN)
AF:
AC:
0
AN:
53398
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111800
Other (OTH)
AF:
AC:
0
AN:
60384
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Hereditary spastic paraplegia 54 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
PhyloP100
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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