8-38253035-CT-CTT
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_015214.3(DDHD2):c.1803dupT(p.Thr602TyrfsTer18) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,002 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
DDHD2
NM_015214.3 frameshift
NM_015214.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.573
Publications
1 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 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 8-38253035-C-CT is Pathogenic according to our data. Variant chr8-38253035-C-CT is described in ClinVar as Pathogenic. ClinVar VariationId is 39676.Status of the report is no_assertion_criteria_provided, 0 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.1803dupT | p.Thr602TyrfsTer18 | frameshift | Exon 15 of 18 | NP_056029.2 | ||
| DDHD2 | NM_001164232.2 | c.1803dupT | p.Thr602TyrfsTer18 | frameshift | Exon 15 of 18 | NP_001157704.1 | |||
| DDHD2 | NM_001362911.2 | c.1803dupT | p.Thr602TyrfsTer18 | frameshift | Exon 15 of 18 | NP_001349840.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DDHD2 | ENST00000397166.7 | TSL:2 MANE Select | c.1803dupT | p.Thr602TyrfsTer18 | frameshift | Exon 15 of 18 | ENSP00000380352.2 | ||
| DDHD2 | ENST00000853787.1 | c.1827dupT | p.Thr610TyrfsTer18 | frameshift | Exon 15 of 18 | ENSP00000523846.1 | |||
| DDHD2 | ENST00000520272.6 | TSL:2 | c.1803dupT | p.Thr602TyrfsTer18 | frameshift | Exon 15 of 18 | ENSP00000429932.2 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152112Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152112
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461890Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727248 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1461890
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
727248
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1112008
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000657 AC: 1AN: 152112Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74300 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152112
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74300
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41430
American (AMR)
AF:
AC:
0
AN:
15254
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3464
East Asian (EAS)
AF:
AC:
0
AN:
5192
South Asian (SAS)
AF:
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
AC:
0
AN:
10596
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68026
Other (OTH)
AF:
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Hereditary spastic paraplegia 54 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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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