rs193922648

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_002294.3(LAMP2):c.-23_-15delGTCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 1,209,919 control chromosomes in the GnomAD database, including 139 homozygotes. There are 6,351 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 8 hom., 382 hem., cov: 22)

Exomes 𝑓: 0.017 ( 131 hom. 5969 hem. )

Consequence

LAMP2
NM_002294.3 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.145

Publications

1 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: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet

LAMP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant X-120469183-AGGCGGCGAC-A is Benign according to our data. Variant chrX-120469183-AGGCGGCGAC-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 36440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0132 (1492/112821) while in subpopulation NFE AF = 0.0196 (1045/53294). AF 95% confidence interval is 0.0186. There are 8 homozygotes in GnomAd4. There are 382 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LAMP2	NM_002294.3 link	c.-23_-15delGTCGCCGCC	5_prime_UTR_variant	Exon 1 of 9	ENST00000200639.9	NP_002285.1	P13473-1
LAMP2	NM_001122606.1 link	c.-23_-15delGTCGCCGCC	5_prime_UTR_variant	Exon 1 of 9		NP_001116078.1	P13473-3
LAMP2	NM_013995.2 link	c.-23_-15delGTCGCCGCC	5_prime_UTR_variant	Exon 1 of 9		NP_054701.1	P13473-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAMP2	ENST00000200639.9 link	c.-23_-15delGTCGCCGCC	5_prime_UTR_variant	Exon 1 of 9	1	NM_002294.3	ENSP00000200639.4	P13473-1
LAMP2	ENST00000434600.6 link	c.-23_-15delGTCGCCGCC	5_prime_UTR_variant	Exon 1 of 9	1		ENSP00000408411.2	P13473-3
LAMP2	ENST00000371335.4 link	c.-23_-15delGTCGCCGCC	5_prime_UTR_variant	Exon 1 of 9	1		ENSP00000360386.4	P13473-2
LAMP2	ENST00000706600.1 link	c.-23_-15delGTCGCCGCC	5_prime_UTR_variant	Exon 1 of 9			ENSP00000516464.1	A0A9L9PXQ4

Frequencies

GnomAD3 genomes

AF:

0.0132

AC:

1493

AN:

112767

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00360

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0133

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.00112

Gnomad SAS

AF:

0.0104

Gnomad FIN

AF:

0.0160

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.0196

Gnomad OTH

AF:

0.0126

GnomAD2 exomes

AF:

0.0147

AC:

2662

AN:

181520

AF XY:

0.0143

show subpopulations

Gnomad AFR exome

AF:

0.00355

Gnomad AMR exome

AF:

0.00984

Gnomad ASJ exome

AF:

0.0147

Gnomad EAS exome

AF:

0.000941

Gnomad FIN exome

AF:

0.0195

Gnomad NFE exome

AF:

0.0186

Gnomad OTH exome

AF:

0.0169

GnomAD4 exome

AF:

0.0167

AC:

18325

AN:

1097098

Hom.:

131

AF XY:

0.0165

AC XY:

5969

AN XY:

362610

show subpopulations

African (AFR)

AF:

0.00417

AC:

110

AN:

26385

American (AMR)

AF:

0.0103

AC:

363

AN:

35187

Ashkenazi Jewish (ASJ)

AF:

0.0146

AC:

283

AN:

19365

East Asian (EAS)

AF:

0.00103

AC:

AN:

30200

South Asian (SAS)

AF:

0.0172

AC:

932

AN:

54118

European-Finnish (FIN)

AF:

0.0211

AC:

854

AN:

40436

Middle Eastern (MID)

AF:

0.0106

AC:

AN:

4073

European-Non Finnish (NFE)

AF:

0.0178

AC:

14965

AN:

841291

Other (OTH)

AF:

0.0162

AC:

744

AN:

46043

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

594

1189

1783

2378

2972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

548

1096

1644

2192

2740

<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:

0.0132

AC:

1492

AN:

112821

Hom.:

Cov.:

AF XY:

0.0109

AC XY:

382

AN XY:

34997

show subpopulations

African (AFR)

AF:

0.00359

AC:

112

AN:

31189

American (AMR)

AF:

0.0132

AC:

142

AN:

10718

Ashkenazi Jewish (ASJ)

AF:

0.0124

AC:

AN:

2660

East Asian (EAS)

AF:

0.00112

AC:

AN:

3561

South Asian (SAS)

AF:

0.0101

AC:

AN:

2770

European-Finnish (FIN)

AF:

0.0160

AC:

AN:

6197

Middle Eastern (MID)

AF:

0.00459

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0196

AC:

1045

AN:

53294

Other (OTH)

AF:

0.0124

AC:

AN:

1533

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

108

161

215

269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0102

Hom.:

Bravo

AF:

0.0127

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 23, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

-23_-15delGTCGCCGCC in exon 1 of LAMP2: This variant is located in the 5?untrans lated region (5?UTR) of the LAMP2 gene. It has not been reported in the literat ure but has been detected by our lab in at least 1% of individuals sequenced. A t this frequency this variant is most likely benign although we cannot exclude a modifying role. -

Danon disease

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 23, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Apr 18, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Primary familial hypertrophic cardiomyopathy

Benign:1

May 20, 2015

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Cardiomyopathy;C0878677:Danon disease

Benign:1

Dec 04, 2012

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The variant is found in HCM panel(s). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.14

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over