Variant 1-15684510-G-GGGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_015164.4(PLEKHM2):c.-37_-35dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.66 ( 31946 hom., cov: 0)

Exomes 𝑓: 0.60 ( 145345 hom. )

Consequence

PLEKHM2
NM_015164.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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 Benign. Variant got -10 ACMG points.

BP6

Variant 1-15684510-G-GGGC is Benign according to our data. Variant chr1-15684510-G-GGGC is described in ClinVar as [Benign]. Clinvar id is 1276290.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
PLEKHM2	NM_015164.4 linkuse as main transcript	c.-37_-35dup	5_prime_UTR_variant	1/20	ENST00000375799.8
PLEKHM2	NM_001410755.1 linkuse as main transcript	c.-37_-35dup	5_prime_UTR_variant	1/19
PLEKHM2	XM_017000757.1 linkuse as main transcript	c.99+2823_99+2825dup	intron_variant
PLEKHM2	XM_017000758.1 linkuse as main transcript	c.99+2823_99+2825dup	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHM2	ENST00000375799.8 linkuse as main transcript	c.-37_-35dup	5_prime_UTR_variant	1/20	1	NM_015164.4	P2	Q8IWE5-1
PLEKHM2	ENST00000375793.2 linkuse as main transcript	c.-37_-35dup	5_prime_UTR_variant	1/19	5		A2	Q8IWE5-2
PLEKHM2	ENST00000642363.1 linkuse as main transcript		upstream_gene_variant				A2
PLEKHM2	ENST00000462455.1 linkuse as main transcript		upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.659

AC:

94867

AN:

143930

Hom.:

31917

Cov.:

show subpopulations

Gnomad AFR

AF:

0.757

Gnomad AMI

AF:

0.689

Gnomad AMR

AF:

0.545

Gnomad ASJ

AF:

0.602

Gnomad EAS

AF:

0.619

Gnomad SAS

AF:

0.480

Gnomad FIN

AF:

0.765

Gnomad MID

AF:

0.555

Gnomad NFE

AF:

0.631

Gnomad OTH

AF:

0.619

GnomAD3 exomes

AF:

0.693

AC:

6854

AN:

9892

Hom.:

2417

AF XY:

0.676

AC XY:

3240

AN XY:

4792

show subpopulations

Gnomad AFR exome

AF:

0.421

Gnomad AMR exome

AF:

0.224

Gnomad ASJ exome

AF:

0.306

Gnomad EAS exome

AF:

0.438

Gnomad SAS exome

AF:

0.303

Gnomad FIN exome

AF:

0.735

Gnomad NFE exome

AF:

0.516

Gnomad OTH exome

AF:

0.510

GnomAD4 exome

AF:

0.597

AC:

495183

AN:

829998

Hom.:

145345

Cov.:

AF XY:

0.596

AC XY:

231920

AN XY:

389264

show subpopulations

Gnomad4 AFR exome

AF:

0.735

Gnomad4 AMR exome

AF:

0.453

Gnomad4 ASJ exome

AF:

0.553

Gnomad4 EAS exome

AF:

0.570

Gnomad4 SAS exome

AF:

0.469

Gnomad4 FIN exome

AF:

0.727

Gnomad4 NFE exome

AF:

0.596

Gnomad4 OTH exome

AF:

0.579

GnomAD4 genome

AF:

0.659

AC:

94923

AN:

143986

Hom.:

31946

Cov.:

AF XY:

0.660

AC XY:

46138

AN XY:

69948

show subpopulations

Gnomad4 AFR

AF:

0.758

Gnomad4 AMR

AF:

0.544

Gnomad4 ASJ

AF:

0.602

Gnomad4 EAS

AF:

0.619

Gnomad4 SAS

AF:

0.479

Gnomad4 FIN

AF:

0.765

Gnomad4 NFE

AF:

0.631

Gnomad4 OTH

AF:

0.621

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 03, 2021

- -

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over