chr9-127935763-CA-TG
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003863.4(DPM2):c.213_214inv(p.Val72Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Y71Y) has been classified as Benign.
Frequency
Genomes: not found (cov: 32)
Consequence
DPM2
NM_003863.4 missense
NM_003863.4 missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.28
Genes affected
DPM2 (HGNC:3006): (dolichyl-phosphate mannosyltransferase subunit 2, regulatory) Dolichol-phosphate mannose (Dol-P-Man) serves as a donor of mannosyl residues on the lumenal side of the endoplasmic reticulum (ER). Lack of Dol-P-Man results in defective surface expression of GPI-anchored proteins. Dol-P-Man is synthesized from GDP-mannose and dolichol-phosphate on the cytosolic side of the ER by the enzyme dolichyl-phosphate mannosyltransferase. The protein encoded by this gene is a hydrophobic protein that contains 2 predicted transmembrane domains and a putative ER localization signal near the C terminus. This protein associates with DPM1 in vivo and is required for the ER localization and stable expression of DPM1 and also enhances the binding of dolichol-phosphate to DPM1. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DPM2 | NM_003863.4 | c.213_214inv | p.Val72Met | missense_variant | 4/4 | ENST00000314392.13 | |
DPM2 | NM_001378437.1 | c.123_124inv | p.Val42Met | missense_variant | 3/3 | ||
DPM2 | NR_165631.1 | n.370_371inv | non_coding_transcript_exon_variant | 4/4 | |||
DPM2 | NR_165632.1 | n.54_55inv | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DPM2 | ENST00000314392.13 | c.213_214inv | p.Val72Met | missense_variant | 4/4 | 1 | NM_003863.4 | P1 | |
ENST00000592240.5 | n.143+1118_143+1119inv | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Congenital muscular dystrophy with intellectual disability and severe epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 23, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with DPM2-related conditions. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 72 of the DPM2 protein (p.Val72Met). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.