chrX-120469179-G-A

Variant names:

Variant summary

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

The NM_002294.3(LAMP2):c.-10C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000752 in 1,210,116 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 32 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., 15 hem., cov: 23)

Exomes 𝑓: 0.000056 ( 0 hom. 17 hem. )

Consequence

LAMP2
NM_002294.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 1.33

Publications

0 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant X-120469179-G-A is Benign according to our data. Variant chrX-120469179-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 138074. Variant chrX-120469179-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 138074. Variant chrX-120469179-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 138074. Variant chrX-120469179-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 138074. Variant chrX-120469179-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 138074. Variant chrX-120469179-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 138074. Variant chrX-120469179-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 138074. Variant chrX-120469179-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 138074. Variant chrX-120469179-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 138074. Variant chrX-120469179-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 138074. Variant chrX-120469179-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 138074. Variant chrX-120469179-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 138074. Variant chrX-120469179-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 138074. Variant chrX-120469179-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 138074. Variant chrX-120469179-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 138074. Variant chrX-120469179-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 138074. Variant chrX-120469179-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 138074. Variant chrX-120469179-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 138074. Variant chrX-120469179-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 138074. Variant chrX-120469179-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 138074. Variant chrX-120469179-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 138074.

BS2

High Hemizygotes in GnomAd4 at 15 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP2	NM_002294.3 link	c.-10C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 9	ENST00000200639.9	NP_002285.1	P13473-1
LAMP2	NM_002294.3 link	c.-10C>T		5_prime_UTR_variant	Exon 1 of 9	ENST00000200639.9	NP_002285.1	P13473-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMP2	ENST00000200639.9 link	c.-10C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 9	1	NM_002294.3	ENSP00000200639.4		P13473-1
LAMP2	ENST00000200639.9 link	c.-10C>T		5_prime_UTR_variant	Exon 1 of 9	1	NM_002294.3	ENSP00000200639.4		P13473-1

Frequencies

GnomAD3 genomes

AF:

0.000267

AC:

AN:

112485

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000321

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00244

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000121

AC:

AN:

181701

AF XY:

0.000105

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000585

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000744

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000556

AC:

AN:

1097631

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

363085

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26396

American (AMR)

AF:

0.000426

AC:

AN:

35196

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19373

East Asian (EAS)

AF:

0.00

AC:

AN:

30204

South Asian (SAS)

AF:

0.00

AC:

AN:

54131

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40465

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4091

European-Non Finnish (NFE)

AF:

0.0000440

AC:

AN:

841718

Other (OTH)

AF:

0.000195

AC:

AN:

46057

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000267

AC:

AN:

112485

Hom.:

Cov.:

AF XY:

0.000433

AC XY:

AN XY:

34631

show subpopulations

African (AFR)

AF:

0.0000321

AC:

AN:

31137

American (AMR)

AF:

0.00244

AC:

AN:

10677

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3572

South Asian (SAS)

AF:

0.00

AC:

AN:

2761

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6153

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000565

AC:

AN:

53098

Other (OTH)

AF:

0.00

AC:

AN:

1515

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000712

Hom.:

Bravo

AF:

0.000332

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:2

Aug 14, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant classified as Uncertain Significance - Favor Benign. The c.-10C>T varian t in LAMP2 has not been previously reported in individuals with cardiomyopathy, but has been identified in 3/46625 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs201209341), including 1 hemizygous individual. This variant is located in the 5' UTR. The c.-10 posit ion is poorly conserved in mammals and evolutionarily distant species and 11 mam mals carry a thymine (T) at this position, raising the possibility that this cha nge may be tolerated. In summary, while the clinical significance of this varian t is uncertain, these data suggest that it is more likely to be benign. -

Apr 02, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Apr 25, 2025

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiomyopathy

Benign:1

Sep 16, 2019

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

1.3

PromoterAI

0.019

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(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

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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