Genetic Variant PLEKHM2:c.-35_-34insCGGGGCGGCGGCGGCGGCGG (chr1-15684510-G-GGGCGGCGGCGGCGGCGGGGC) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_015164.4(PLEKHM2):c.-35_-34insCGGGGCGGCGGCGGCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PLEKHM2
NM_015164.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0330

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
PLEKHM2	NM_015164.4 link	c.-35_-34insCGGGGCGGCGGCGGCGGCGG	5_prime_UTR_variant	Exon 1 of 20	ENST00000375799.8	NP_055979.2
PLEKHM2	NM_001410755.1 link	c.-35_-34insCGGGGCGGCGGCGGCGGCGG	5_prime_UTR_variant	Exon 1 of 19		NP_001397684.1
PLEKHM2	XM_017000757.1 link	c.99+2825_99+2826insCGGGGCGGCGGCGGCGGCGG	intron_variant	Intron 1 of 19		XP_016856246.1
PLEKHM2	XM_017000758.1 link	c.99+2825_99+2826insCGGGGCGGCGGCGGCGGCGG	intron_variant	Intron 1 of 18		XP_016856247.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLEKHM2	ENST00000375799 link	c.-35_-34insCGGGGCGGCGGCGGCGGCGG	5_prime_UTR_variant	Exon 1 of 20	1	NM_015164.4	ENSP00000364956.3	Q8IWE5-1
PLEKHM2	ENST00000375793 link	c.-35_-34insCGGGGCGGCGGCGGCGGCGG	5_prime_UTR_variant	Exon 1 of 19	5		ENSP00000364950.2	Q8IWE5-2
PLEKHM2	ENST00000642363.1 link	c.-49_-48insGGCGGCGGCGGCGGCGGGGC	upstream_gene_variant				ENSP00000494591.1	A0A2R8Y575
PLEKHM2	ENST00000462455.1 link	n.-31_-30insGGCGGCGGCGGCGGCGGGGC	upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000139

AC:

AN:

144046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000308

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000360

AC:

AN:

832706

Hom.:

Cov.:

AF XY:

0.00000256

AC XY:

AN XY:

390530

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000589

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000272

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000139

AC:

AN:

144102

Hom.:

Cov.:

AF XY:

0.0000143

AC XY:

AN XY:

70004

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000308

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

1-15684510-GGGCGGC-GGGCGGCGGCGGCGGCGGGGCGGCGGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over