Genetic Variant PLEKHM2:c.60+80_60+81insCGAACCTGCTGCCGCAGGGACTCG (chr1-15684697-G-GGCGAACCTGCTGCCGCAGGGACTC) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015164.4(PLEKHM2):c.60+80_60+81insCGAACCTGCTGCCGCAGGGACTCG variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PLEKHM2
NM_015164.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.02

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AR Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics

PLEKHM2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.60+80_60+81insCGAACCTGCTGCCGCAGGGACTCG		intron	N/A	NP_055979.2	Q8IWE5-1
	PLEKHM2	NM_001410755.1		c.60+80_60+81insCGAACCTGCTGCCGCAGGGACTCG		intron	N/A	NP_001397684.1	Q8IWE5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLEKHM2	ENST00000375799.8	TSL:1 MANE Select	c.60+79_60+80insGCGAACCTGCTGCCGCAGGGACTC	intron	N/A	ENSP00000364956.3	Q8IWE5-1
PLEKHM2	ENST00000957356.1		c.60+79_60+80insGCGAACCTGCTGCCGCAGGGACTC	intron	N/A	ENSP00000627415.1
PLEKHM2	ENST00000957353.1		c.60+79_60+80insGCGAACCTGCTGCCGCAGGGACTC	intron	N/A	ENSP00000627412.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

644948

Hom.:

AF XY:

0.00

AC XY:

AN XY:

308400

African (AFR)

AF:

0.00

AC:

AN:

13106

American (AMR)

AF:

0.00

AC:

AN:

4464

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7530

East Asian (EAS)

AF:

0.00

AC:

AN:

15648

South Asian (SAS)

AF:

0.00

AC:

AN:

11966

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1978

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

537354

Other (OTH)

AF:

0.00

AC:

AN:

24508

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.0

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over