chr1-15684510-G-GGGC

Position:

• chr1-15684510-G-GGGC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0330

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHM2	NM_015164.4	c.-37_-35dup		5_prime_UTR_variant	1/20	ENST00000375799.8	NP_055979.2
PLEKHM2	NM_001410755.1	c.-37_-35dup		5_prime_UTR_variant	1/19		NP_001397684.1
PLEKHM2	XM_017000757.1	c.99+2823_99+2825dup		intron_variant			XP_016856246.1
PLEKHM2	XM_017000758.1	c.99+2823_99+2825dup		intron_variant			XP_016856247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHM2	ENST00000375799.8	c.-37_-35dup		5_prime_UTR_variant	1/20	1	NM_015164.4	ENSP00000364956	P2
PLEKHM2	ENST00000375793.2	c.-37_-35dup		5_prime_UTR_variant	1/19	5		ENSP00000364950	A2
PLEKHM2	ENST00000642363.1			upstream_gene_variant				ENSP00000494591	A2
PLEKHM2	ENST00000462455.1			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.659 AC: 94867 AN: 143930 Hom.: 31917 Cov.: 0

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

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.: 17 AF XY: 0.596 AC XY: 231920 AN XY: 389264

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.: 0 AF XY: 0.660 AC XY: 46138 AN XY: 69948

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 03, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs767880122; hg19: chr1-16011005;