X-120439186-T-C
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The ENST00000371335.4(LAMP2):āc.1201A>Gā(p.Arg401Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000188 in 1,208,176 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 70 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000080 ( 0 hom., 2 hem., cov: 24)
Exomes š: 0.00020 ( 0 hom. 68 hem. )
Consequence
LAMP2
ENST00000371335.4 missense
ENST00000371335.4 missense
Scores
2
7
4
Clinical Significance
Conservation
PhyloP100: 5.76
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 GnomAd4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LAMP2 | NM_002294.3 | c.1093+2544A>G | intron_variant | ENST00000200639.9 | NP_002285.1 | |||
LAMP2 | NM_013995.2 | c.1201A>G | p.Arg401Gly | missense_variant | 9/9 | NP_054701.1 | ||
LAMP2 | NM_001122606.1 | c.1093+2544A>G | intron_variant | NP_001116078.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMP2 | ENST00000200639.9 | c.1093+2544A>G | intron_variant | 1 | NM_002294.3 | ENSP00000200639 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000803 AC: 9AN: 112043Hom.: 0 Cov.: 24 AF XY: 0.0000585 AC XY: 2AN XY: 34203
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GnomAD3 exomes AF: 0.0000545 AC: 10AN: 183391Hom.: 0 AF XY: 0.0000737 AC XY: 5AN XY: 67869
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GnomAD4 exome AF: 0.000199 AC: 218AN: 1096133Hom.: 0 Cov.: 28 AF XY: 0.000188 AC XY: 68AN XY: 361579
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GnomAD4 genome AF: 0.0000803 AC: 9AN: 112043Hom.: 0 Cov.: 24 AF XY: 0.0000585 AC XY: 2AN XY: 34203
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Danon disease Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 09, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 12, 2021 | - - |
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 22, 2022 | Located in an alternate transcript of the LAMP2 gene and has been reported previously as an isoform-specific variant; however, no additional information regarding the phenotype or the variant was provided (D'souza et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25228319) - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | LAMP2: BP4, BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MVP
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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