Genetic Variant PLEKHM2:c.-37_-35dupCGG (chr1-15684510-G-GGGC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_015164.4(PLEKHM2):c.-37_-35dupCGG 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

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: Ambry Genetics, ClinGen

PLEKHM2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_015164.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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.-37_-35dupCGG		5_prime_UTR	Exon 1 of 20	NP_055979.2	Q8IWE5-1
	PLEKHM2	NM_001410755.1		c.-37_-35dupCGG		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.-37_-35dupCGG	5_prime_UTR	Exon 1 of 20	ENSP00000364956.3	Q8IWE5-1
PLEKHM2	ENST00000957353.1		c.-37_-35dupCGG	5_prime_UTR	Exon 1 of 20	ENSP00000627412.1
PLEKHM2	ENST00000957355.1		c.-37_-35dupCGG	5_prime_UTR	Exon 1 of 20	ENSP00000627414.1

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

GnomAD2 exomes

AF:

0.693

AC:

6854

AN:

9892

AF XY:

0.676

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 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

African (AFR)

AF:

0.735

AC:

11200

AN:

15244

American (AMR)

AF:

0.453

AC:

1155

AN:

2552

Ashkenazi Jewish (ASJ)

AF:

0.553

AC:

3563

AN:

6442

East Asian (EAS)

AF:

0.570

AC:

4555

AN:

7990

South Asian (SAS)

AF:

0.469

AC:

7938

AN:

16924

European-Finnish (FIN)

AF:

0.727

AC:

13220

AN:

18188

Middle Eastern (MID)

AF:

0.496

AC:

988

AN:

1990

European-Non Finnish (NFE)

AF:

0.596

AC:

436245

AN:

732498

Other (OTH)

AF:

0.579

AC:

16319

AN:

28170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

8540

17080

25619

34159

42699

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15736

31472

47208

62944

78680

<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:

0.659

AC:

94923

AN:

143986

Hom.:

31946

Cov.:

AF XY:

0.660

AC XY:

46138

AN XY:

69948

show subpopulations

African (AFR)

AF:

0.758

AC:

30457

AN:

40196

American (AMR)

AF:

0.544

AC:

7978

AN:

14656

Ashkenazi Jewish (ASJ)

AF:

0.602

AC:

2028

AN:

3368

East Asian (EAS)

AF:

0.619

AC:

2956

AN:

4776

South Asian (SAS)

AF:

0.479

AC:

2275

AN:

4746

European-Finnish (FIN)

AF:

0.765

AC:

6246

AN:

8160

Middle Eastern (MID)

AF:

0.567

AC:

161

AN:

284

European-Non Finnish (NFE)

AF:

0.631

AC:

40973

AN:

64918

Other (OTH)

AF:

0.621

AC:

1247

AN:

2008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1545

3090

4636

6181

7726

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

744

1488

2232

2976

3720

<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:

0.371

Hom.:

1087

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.033

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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-GGGCGGCGGC

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