rs149155417
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_002294.3(LAMP2):c.741+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000617 in 1,192,854 control chromosomes in the GnomAD database, including 10 homozygotes. There are 230 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.00043 ( 0 hom., 13 hem., cov: 23)
Exomes 𝑓: 0.00064 ( 10 hom. 217 hem. )
Consequence
LAMP2
NM_002294.3 intron
NM_002294.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.29
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant X-120447830-G-A is Benign according to our data. Variant chrX-120447830-G-A is described in ClinVar as [Benign]. Clinvar id is 44436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-120447830-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000637 (688/1080332) while in subpopulation EAS AF= 0.0218 (658/30121). AF 95% confidence interval is 0.0205. There are 10 homozygotes in gnomad4_exome. There are 217 alleles in male gnomad4_exome subpopulation. Median coverage is 28. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd4 at 13 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMP2 | NM_002294.3 | c.741+11C>T | intron_variant | ENST00000200639.9 | |||
LAMP2 | NM_001122606.1 | c.741+11C>T | intron_variant | ||||
LAMP2 | NM_013995.2 | c.741+11C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMP2 | ENST00000200639.9 | c.741+11C>T | intron_variant | 1 | NM_002294.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000427 AC: 48AN: 112466Hom.: 0 Cov.: 23 AF XY: 0.000376 AC XY: 13AN XY: 34620
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GnomAD3 exomes AF: 0.00101 AC: 185AN: 182348Hom.: 0 AF XY: 0.000911 AC XY: 61AN XY: 66932
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GnomAD4 exome AF: 0.000637 AC: 688AN: 1080332Hom.: 10 Cov.: 28 AF XY: 0.000624 AC XY: 217AN XY: 347986
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 20, 2012 | 741+11C>T in intron 5 of LAMP2: This variant is not expected to have clinical si gnificance because it has been identified in 2.1% (9/428) Asian chromosomes from a broad population by the 1000 Genomes project (dbSNP rs149155417). - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 04, 2019 | Variant summary: LAMP2 c.741+11C>T alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.001 in 182348 control chromosomes (gnomAD). The observed variant frequency is approximately 81 fold of the estimated maximal expected allele frequency for a pathogenic variant in LAMP2 causing Cardiomyopathy phenotype (1.3e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.741+11C>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Danon disease Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at