chrX-120439216-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_013995.2(LAMP2):c.1171G>A(p.Val391Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00681 in 1,207,482 control chromosomes in the GnomAD database, including 24 homozygotes. There are 2,640 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0039 ( 0 hom., 111 hem., cov: 23)

Exomes 𝑓: 0.0071 ( 24 hom. 2529 hem. )

Consequence

LAMP2
NM_013995.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:16

Conservation

PhyloP100: 5.91

Publications

8 publications found

Variant links:

Genes affected

LAMP2 (HGNC:6501): (lysosomal associated membrane protein 2) The protein encoded by this gene is a member of a family of membrane glycoproteins. This glycoprotein provides selectins with carbohydrate ligands. It may play a role in tumor cell metastasis. It may also function in the protection, maintenance, and adhesion of the lysosome. Alternative splicing of this gene results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2008]

LAMP2 Gene-Disease associations (from GenCC):

Danon disease
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp

LAMP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050724447).

BP6

Variant X-120439216-C-T is Benign according to our data. Variant chrX-120439216-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 45573.

BS2

High Hemizygotes in GnomAd4 at 111 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013995.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LAMP2	NM_002294.3	MANE Select	c.1093+2514G>A		intron	N/A	NP_002285.1	P13473-1
LAMP2	NM_013995.2		c.1171G>A	p.Val391Ile	missense	Exon 9 of 9	NP_054701.1	P13473-2
LAMP2	NM_001122606.1		c.1093+2514G>A		intron	N/A	NP_001116078.1	P13473-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LAMP2	ENST00000371335.4	TSL:1	c.1171G>A	p.Val391Ile	missense	Exon 9 of 9	ENSP00000360386.4	P13473-2
LAMP2	ENST00000200639.9	TSL:1 MANE Select	c.1093+2514G>A		intron	N/A	ENSP00000200639.4	P13473-1
LAMP2	ENST00000434600.6	TSL:1	c.1093+2514G>A		intron	N/A	ENSP00000408411.2	P13473-3

Frequencies

GnomAD3 genomes

AF:

0.00394

AC:

440

AN:

111597

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000814

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00151

Gnomad EAS

AF:

0.000834

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00235

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.00696

Gnomad OTH

AF:

0.00465

GnomAD2 exomes

AF:

0.00387

AC:

709

AN:

183335

AF XY:

0.00458

show subpopulations

Gnomad AFR exome

AF:

0.000684

Gnomad AMR exome

AF:

0.000766

Gnomad ASJ exome

AF:

0.000668

Gnomad EAS exome

AF:

0.000289

Gnomad FIN exome

AF:

0.00137

Gnomad NFE exome

AF:

0.00685

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00711

AC:

7787

AN:

1095836

Hom.:

Cov.:

AF XY:

0.00700

AC XY:

2529

AN XY:

361326

show subpopulations

African (AFR)

AF:

0.000455

AC:

AN:

26354

American (AMR)

AF:

0.000909

AC:

AN:

35204

Ashkenazi Jewish (ASJ)

AF:

0.00108

AC:

AN:

19364

East Asian (EAS)

AF:

0.0000663

AC:

AN:

30152

South Asian (SAS)

AF:

0.00412

AC:

223

AN:

54096

European-Finnish (FIN)

AF:

0.00210

AC:

AN:

40524

Middle Eastern (MID)

AF:

0.000968

AC:

AN:

4131

European-Non Finnish (NFE)

AF:

0.00845

AC:

7096

AN:

839993

Other (OTH)

AF:

0.00678

AC:

312

AN:

46018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

272

544

815

1087

1359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

284

568

852

1136

1420

<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:

0.00394

AC:

440

AN:

111646

Hom.:

Cov.:

AF XY:

0.00328

AC XY:

111

AN XY:

33892

show subpopulations

African (AFR)

AF:

0.000812

AC:

AN:

30774

American (AMR)

AF:

0.00105

AC:

AN:

10455

Ashkenazi Jewish (ASJ)

AF:

0.00151

AC:

AN:

2649

East Asian (EAS)

AF:

0.000837

AC:

AN:

3584

South Asian (SAS)

AF:

0.00187

AC:

AN:

2671

European-Finnish (FIN)

AF:

0.00235

AC:

AN:

5963

Middle Eastern (MID)

AF:

0.00459

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00696

AC:

370

AN:

53123

Other (OTH)

AF:

0.00460

AC:

AN:

1523

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00560

Hom.:

240

Bravo

AF:

0.00356

TwinsUK

AF:

0.0108

AC:

ALSPAC

AF:

0.00900

AC:

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00654

AC:

ExAC

AF:

0.00426

AC:

517

EpiCase

AF:

0.00758

EpiControl

AF:

0.00818

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

not provided (4)

Danon disease (3)

Cardiovascular phenotype (1)

Hypertrophic cardiomyopathy (1)

LAMP2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.54

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.66

M_CAP

Benign

0.0031

MetaRNN

Benign

0.0051

MetaSVM

Benign

-0.98

PhyloP100

5.9

PROVEAN

Benign

0.43

REVEL

Benign

0.085

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0030

Vest4

0.077

MVP

0.44

ClinPred

0.019

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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.

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