rs193922648

Positions:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 36440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-120469183-AGGCGGCGAC-A is described in Lovd as [Likely_pathogenic]. Variant chrX-120469183-AGGCGGCGAC-A is described in Lovd as [Benign]. Variant chrX-120469183-AGGCGGCGAC-A is described in Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
LAMP2	NM_002294.3 linkuse as main transcript	c.-23_-15delGTCGCCGCC	5_prime_UTR_variant	1/9	ENST00000200639.9	NP_002285.1	P13473-1
LAMP2	NM_001122606.1 linkuse as main transcript	c.-23_-15delGTCGCCGCC	5_prime_UTR_variant	1/9		NP_001116078.1	P13473-3
LAMP2	NM_013995.2 linkuse as main transcript	c.-23_-15delGTCGCCGCC	5_prime_UTR_variant	1/9		NP_054701.1	P13473-2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LAMP2	ENST00000200639.9 linkuse as main transcript	c.-23_-15delGTCGCCGCC	5_prime_UTR_variant	1/9	1	NM_002294.3	ENSP00000200639.4	P13473-1
LAMP2	ENST00000434600.6 linkuse as main transcript	c.-23_-15delGTCGCCGCC	5_prime_UTR_variant	1/9	1		ENSP00000408411.2	P13473-3
LAMP2	ENST00000371335.4 linkuse as main transcript	c.-23_-15delGTCGCCGCC	5_prime_UTR_variant	1/9	1		ENSP00000360386.4	P13473-2
LAMP2	ENST00000706600.1 linkuse as main transcript	c.-23_-15delGTCGCCGCC	5_prime_UTR_variant	1/9			ENSP00000516464.1	A0A9L9PXQ4

Frequencies

GnomAD3 genomes

AF:

0.0132

AC:

1493

AN:

112767

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

383

AN XY:

34933

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

GnomAD3 exomes

AF:

0.0147

AC:

2662

AN:

181520

Hom.:

AF XY:

0.0143

AC XY:

957

AN XY:

66892

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 SAS exome

AF:

0.0179

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

Gnomad4 AFR exome

AF:

0.00417

Gnomad4 AMR exome

AF:

0.0103

Gnomad4 ASJ exome

AF:

0.0146

Gnomad4 EAS exome

AF:

0.00103

Gnomad4 SAS exome

AF:

0.0172

Gnomad4 FIN exome

AF:

0.0211

Gnomad4 NFE exome

AF:

0.0178

Gnomad4 OTH exome

AF:

0.0162

GnomAD4 genome

AF:

0.0132

AC:

1492

AN:

112821

Hom.:

Cov.:

AF XY:

0.0109

AC XY:

382

AN XY:

34997

show subpopulations

Gnomad4 AFR

AF:

0.00359

Gnomad4 AMR

AF:

0.0132

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.00112

Gnomad4 SAS

AF:

0.0101

Gnomad4 FIN

AF:

0.0160

Gnomad4 NFE

AF:

0.0196

Gnomad4 OTH

AF:

0.0124

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

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 23, 2011	-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. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Danon disease

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 23, 2023	- -

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Apr 18, 2017

- -

Primary familial hypertrophic cardiomyopathy

Benign:1

Benign, no assertion criteria provided

clinical testing

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

May 20, 2015

- -

Cardiomyopathy;C0878677:Danon disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 04, 2012

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over