rs727504957
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_002294.3(LAMP2):c.1211A>T(p.His404Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,096,450 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000055 ( 0 hom. 4 hem. )
Consequence
LAMP2
NM_002294.3 missense
NM_002294.3 missense
Scores
1
4
12
Clinical Significance
Conservation
PhyloP100: 0.951
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 Likely_benign. Variant got -4 ACMG points.
BS2
?
High Hemizygotes in GnomAdExome4 at 4 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMP2 | NM_002294.3 | c.1211A>T | p.His404Leu | missense_variant | 9/9 | ENST00000200639.9 | |
LAMP2 | NM_001122606.1 | c.1094-2719A>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMP2 | ENST00000200639.9 | c.1211A>T | p.His404Leu | missense_variant | 9/9 | 1 | NM_002294.3 | P3 | |
LAMP2 | ENST00000434600.6 | c.1094-2719A>T | intron_variant | 1 | A1 | ||||
LAMP2 | ENST00000706600.1 | c.*1070A>T | 3_prime_UTR_variant | 9/9 | |||||
LAMP2 | ENST00000486593.5 | c.*196A>T | 3_prime_UTR_variant, NMD_transcript_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD3 exomes AF: 0.00000551 AC: 1AN: 181378Hom.: 0 AF XY: 0.0000149 AC XY: 1AN XY: 67212
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GnomAD4 exome AF: 0.00000547 AC: 6AN: 1096450Hom.: 0 Cov.: 29 AF XY: 0.0000110 AC XY: 4AN XY: 362028
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GnomAD4 genome ? Cov.: 23
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Cov.:
23
Bravo
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 10, 2014 | The p.His404Leu variant in LAMP2 has been identified by our laboratory in 1 adul t with non-ischemic cardiomyopathy, hypokinesis, and T-wave abnormalities; howev er, this individual also carried a pathogenic variant in another gene. It was ab sent from large population studies. Computational prediction tools and conservat ion analysis do not provide strong support for or against an impact the protein. In summary, the clinical significance of the p.His404Leu variant is uncertain. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
CardioboostCm
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Uncertain
T
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
N;N;N
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of catalytic residue at H404 (P = 0.0309);
MVP
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
Splicing
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Calibrated prediction
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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