Genetic Variant PLEKHM2:c.-43_-35dupCGGCGGCGG (chr1-15684510-G-GGGCGGCGGC) – 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.-43_-35dupCGGCGGCGG 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 0.00096 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00049 ( 0 hom. )

Consequence

PLEKHM2
NM_015164.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0330

Publications

2 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:

Genome browser will be placed here

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.-43_-35dupCGGCGGCGG		5_prime_UTR	Exon 1 of 20	NP_055979.2	Q8IWE5-1
	PLEKHM2	NM_001410755.1		c.-43_-35dupCGGCGGCGG		5_prime_UTR	Exon 1 of 19	NP_001397684.1	Q8IWE5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLEKHM2	ENST00000375799.8	TSL:1 MANE Select	c.-43_-35dupCGGCGGCGG	5_prime_UTR	Exon 1 of 20	ENSP00000364956.3	Q8IWE5-1
PLEKHM2	ENST00000957353.1		c.-43_-35dupCGGCGGCGG	5_prime_UTR	Exon 1 of 20	ENSP00000627412.1
PLEKHM2	ENST00000957355.1		c.-43_-35dupCGGCGGCGG	5_prime_UTR	Exon 1 of 20	ENSP00000627414.1

Frequencies

GnomAD3 genomes

AF:

0.000965

AC:

139

AN:

144046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000274

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000683

Gnomad ASJ

AF:

0.00178

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00551

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00114

Gnomad OTH

AF:

0.00100

GnomAD2 exomes

AF:

0.00313

AC:

AN:

9892

AF XY:

0.00292

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00360

Gnomad NFE exome

AF:

0.000980

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000491

AC:

409

AN:

832674

Hom.:

Cov.:

AF XY:

0.000487

AC XY:

190

AN XY:

390518

show subpopulations

African (AFR)

AF:

0.000392

AC:

AN:

15288

American (AMR)

AF:

0.00

AC:

AN:

2566

Ashkenazi Jewish (ASJ)

AF:

0.00155

AC:

AN:

6458

East Asian (EAS)

AF:

0.00

AC:

AN:

8036

South Asian (SAS)

AF:

0.00

AC:

AN:

16992

European-Finnish (FIN)

AF:

0.00334

AC:

AN:

18290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2002

European-Non Finnish (NFE)

AF:

0.000438

AC:

322

AN:

734758

Other (OTH)

AF:

0.000354

AC:

AN:

28284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000965

AC:

139

AN:

144102

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

AN XY:

70004

show subpopulations

African (AFR)

AF:

0.000274

AC:

AN:

40218

American (AMR)

AF:

0.0000682

AC:

AN:

14666

Ashkenazi Jewish (ASJ)

AF:

0.00178

AC:

AN:

3370

East Asian (EAS)

AF:

0.00

AC:

AN:

4780

South Asian (SAS)

AF:

0.00

AC:

AN:

4746

European-Finnish (FIN)

AF:

0.00551

AC:

AN:

8174

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00114

AC:

AN:

64978

Other (OTH)

AF:

0.000995

AC:

AN:

2010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00443

Hom.:

1087

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.033

Mutation Taster

=300/0

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

1-15684510-GGGCGGC-GGGCGGCGGCGGCGGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over