chrX-120469179-G-A

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

2

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

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
LAMP2NM_002294.3 linkc.-10C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 9 ENST00000200639.9 NP_002285.1 P13473-1
LAMP2NM_002294.3 linkc.-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
LAMP2ENST00000200639.9 linkc.-10C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 9 1 NM_002294.3 ENSP00000200639.4 P13473-1
LAMP2ENST00000200639.9 linkc.-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:
30
AN:
112485
Hom.:
0
Cov.:
23
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:
22
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:
61
AN:
1097631
Hom.:
0
Cov.:
30
AF XY:
0.0000468
AC XY:
17
AN XY:
363085
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
26396
American (AMR)
AF:
0.000426
AC:
15
AN:
35196
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19373
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30204
South Asian (SAS)
AF:
0.00
AC:
0
AN:
54131
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
40465
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4091
European-Non Finnish (NFE)
AF:
0.0000440
AC:
37
AN:
841718
Other (OTH)
AF:
0.000195
AC:
9
AN:
46057
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.474
Heterozygous variant carriers
0
2
4
7
9
11
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
2
4
6
8
10
<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:
30
AN:
112485
Hom.:
0
Cov.:
23
AF XY:
0.000433
AC XY:
15
AN XY:
34631
show subpopulations
African (AFR)
AF:
0.0000321
AC:
1
AN:
31137
American (AMR)
AF:
0.00244
AC:
26
AN:
10677
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2651
East Asian (EAS)
AF:
0.00
AC:
0
AN:
3572
South Asian (SAS)
AF:
0.00
AC:
0
AN:
2761
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
6153
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
239
European-Non Finnish (NFE)
AF:
0.0000565
AC:
3
AN:
53098
Other (OTH)
AF:
0.00
AC:
0
AN:
1515
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.438
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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.:
0
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
12
DANN
Benign
0.92
PhyloP100
1.3
PromoterAI
0.019
Neutral
Mutation Taster
=300/0
polymorphism

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

Other links and lift over

dbSNP: rs201209341; hg19: chrX-119603034; API