rs199666070
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_015164.4(PLEKHM2):c.162G>A(p.Leu54Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000075 in 1,586,276 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 Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L54L) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000049 ( 0 hom. )
Consequence
PLEKHM2
NM_015164.4 synonymous
NM_015164.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.02
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
Variant 1-15716338-G-A is Benign according to our data. Variant chr1-15716338-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 478070.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.02 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PLEKHM2 | NM_015164.4 | c.162G>A | p.Leu54Leu | synonymous_variant | Exon 2 of 20 | ENST00000375799.8 | NP_055979.2 | |
| PLEKHM2 | NM_001410755.1 | c.162G>A | p.Leu54Leu | synonymous_variant | Exon 2 of 19 | NP_001397684.1 | ||
| PLEKHM2 | XM_017000757.1 | c.201G>A | p.Leu67Leu | synonymous_variant | Exon 2 of 20 | XP_016856246.1 | ||
| PLEKHM2 | XM_017000758.1 | c.201G>A | p.Leu67Leu | synonymous_variant | Exon 2 of 19 | XP_016856247.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| PLEKHM2 | ENST00000375799.8 | c.162G>A | p.Leu54Leu | synonymous_variant | Exon 2 of 20 | 1 | NM_015164.4 | ENSP00000364956.3 | ||
| PLEKHM2 | ENST00000375793.2 | c.162G>A | p.Leu54Leu | synonymous_variant | Exon 2 of 19 | 5 | ENSP00000364950.2 | |||
| PLEKHM2 | ENST00000642363.1 | c.162G>A | p.Leu54Leu | synonymous_variant | Exon 2 of 21 | ENSP00000494591.1 | ||||
| PLEKHM2 | ENST00000462455.1 | n.180G>A | non_coding_transcript_exon_variant | Exon 2 of 5 | 5 |
Frequencies
GnomAD3 genomes 0.000309 AC: 47AN: 152106Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000740 AC: 16AN: 216238Hom.: 0 AF XY: 0.0000344 AC XY: 4AN XY: 116370
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GnomAD4 exome AF: 0.0000488 AC: 70AN: 1434052Hom.: 0 Cov.: 29 AF XY: 0.0000492 AC XY: 35AN XY: 711878
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GnomAD4 genome 0.000322 AC: 49AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20AN XY: 74420
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Dilated Cardiomyopathy, Recessive Benign:1
Dec 24, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at