1-15684697-G-GGCGACCCTGCTGCCGCAGGGACTC

Position:

• chr1-15684697-G-GGCGACCCTGCTGCCGCAGGGACTC

Variant summary

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

The NM_015164.4(PLEKHM2):​c.60+80_60+81insCGACCCTGCTGCCGCAGGGACTCG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 794,356 control chromosomes in the GnomAD database, including 38,002 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (13259 hom., cov: 0)
  • Exomes 𝑓: 0.25 (24743 hom.)
• Consequence: PLEKHM2 NM_015164.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.02

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 1-15684697-G-GGCGACCCTGCTGCCGCAGGGACTC is Benign according to our data. Variant chr1-15684697-G-GGCGACCCTGCTGCCGCAGGGACTC is described in ClinVar as [Benign]. Clinvar id is 1231190.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHM2	NM_015164.4	c.60+80_60+81insCGACCCTGCTGCCGCAGGGACTCG		intron_variant		ENST00000375799.8	NP_055979.2
PLEKHM2	NM_001410755.1	c.60+80_60+81insCGACCCTGCTGCCGCAGGGACTCG		intron_variant			NP_001397684.1
PLEKHM2	XM_017000757.1	c.99+2999_99+3000insCGACCCTGCTGCCGCAGGGACTCG		intron_variant			XP_016856246.1
PLEKHM2	XM_017000758.1	c.99+2999_99+3000insCGACCCTGCTGCCGCAGGGACTCG		intron_variant			XP_016856247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHM2	ENST00000375799.8	c.60+80_60+81insCGACCCTGCTGCCGCAGGGACTCG		intron_variant		1	NM_015164.4	ENSP00000364956	P2
PLEKHM2	ENST00000375793.2	c.60+80_60+81insCGACCCTGCTGCCGCAGGGACTCG		intron_variant		5		ENSP00000364950	A2
PLEKHM2	ENST00000642363.1	c.60+80_60+81insCGACCCTGCTGCCGCAGGGACTCG		intron_variant				ENSP00000494591	A2
PLEKHM2	ENST00000462455.1	n.78+80_78+81insCGACCCTGCTGCCGCAGGGACTCG		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55054 AN: 150178 Hom.: 13216 Cov.: 0

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.0309

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.351

GnomAD4 exome AF: 0.250 AC: 160789 AN: 644070 Hom.: 24743 AF XY: 0.249 AC XY: 76740 AN XY: 307976

Gnomad4 AFR exome AF: 0.710

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.290

Gnomad4 EAS exome AF: 0.0594

Gnomad4 SAS exome AF: 0.217

Gnomad4 FIN exome AF: 0.287

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.253

GnomAD4 genome AF: 0.367 AC: 55152 AN: 150286 Hom.: 13259 Cov.: 0 AF XY: 0.362 AC XY: 26571 AN XY: 73368

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.0308

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.352

Alfa AF: 0.0943 Hom.: 171

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

Aug 03, 2020

- -

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: rs369410677; hg19: chr1-16011192;