rs767880122
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_015164.4(PLEKHM2):c.-40_-35delCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000841 in 832,692 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 0)
Exomes 𝑓: 0.0000084 ( 1 hom. )
Consequence
PLEKHM2
NM_015164.4 5_prime_UTR
NM_015164.4 5_prime_UTR
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.20
Publications
2 publications found
Genes affected
PLEKHM2 (HGNC:29131): (pleckstrin homology and RUN domain containing M2) This gene encodes a protein that binds the plus-end directed microtubule motor protein kinesin, together with the lysosomal GTPase Arl8, and is required for lysosomes to distribute away from the microtubule-organizing center. The encoded protein belongs to the multisubunit BLOC-one-related complex that regulates lysosome positioning. It binds a Salmonella effector protein called Salmonella induced filament A and is a critical host determinant in Salmonella pathogenesis. It has a domain architecture consisting of an N-terminal RPIP8, UNC-14, and NESCA (RUN) domain that binds kinesin-1 as well as the lysosomal GTPase Arl8, and a C-terminal pleckstrin homology domain that binds the Salmonella induced filament A effector protein. Naturally occurring mutations in this gene lead to abnormal localization of lysosomes, impaired autophagy flux and are associated with recessive dilated cardiomyopathy and left ventricular noncompaction. [provided by RefSeq, Feb 2017]
PLEKHM2 Gene-Disease associations (from GenCC):
- dilated cardiomyopathyInheritance: AR Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_015164.4. 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 |
|---|---|---|---|---|---|---|---|---|---|
| PLEKHM2 | NM_015164.4 | MANE Select | c.-40_-35delCGGCGG | 5_prime_UTR | Exon 1 of 20 | NP_055979.2 | Q8IWE5-1 | ||
| PLEKHM2 | NM_001410755.1 | c.-40_-35delCGGCGG | 5_prime_UTR | Exon 1 of 19 | NP_001397684.1 | Q8IWE5-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PLEKHM2 | ENST00000375799.8 | TSL:1 MANE Select | c.-40_-35delCGGCGG | 5_prime_UTR | Exon 1 of 20 | ENSP00000364956.3 | Q8IWE5-1 | ||
| PLEKHM2 | ENST00000957353.1 | c.-40_-35delCGGCGG | 5_prime_UTR | Exon 1 of 20 | ENSP00000627412.1 | ||||
| PLEKHM2 | ENST00000957355.1 | c.-40_-35delCGGCGG | 5_prime_UTR | Exon 1 of 20 | ENSP00000627414.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
0
GnomAD4 exome AF: 0.00000841 AC: 7AN: 832692Hom.: 1 AF XY: 0.00000768 AC XY: 3AN XY: 390524 show subpopulations
GnomAD4 exome
AF:
AC:
7
AN:
832692
Hom.:
AF XY:
AC XY:
3
AN XY:
390524
show subpopulations
African (AFR)
AF:
AC:
0
AN:
15288
American (AMR)
AF:
AC:
0
AN:
2566
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
6460
East Asian (EAS)
AF:
AC:
0
AN:
8036
South Asian (SAS)
AF:
AC:
0
AN:
16992
European-Finnish (FIN)
AF:
AC:
0
AN:
18302
Middle Eastern (MID)
AF:
AC:
0
AN:
2002
European-Non Finnish (NFE)
AF:
AC:
7
AN:
734762
Other (OTH)
AF:
AC:
0
AN:
28284
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
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2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
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8
10
<30
30-35
35-40
40-45
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50-55
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
0
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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