rs117800773
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000428.3(LTBP2):c.4516G>A(p.Val1506Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 1,614,118 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000428.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LTBP2 | NM_000428.3 | c.4516G>A | p.Val1506Met | missense_variant | 31/36 | ENST00000261978.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LTBP2 | ENST00000261978.9 | c.4516G>A | p.Val1506Met | missense_variant | 31/36 | 1 | NM_000428.3 | P1 | |
LTBP2 | ENST00000556690.5 | c.4384G>A | p.Val1462Met | missense_variant | 30/35 | 5 | |||
LTBP2 | ENST00000553939.5 | c.4516G>A | p.Val1506Met | missense_variant, NMD_transcript_variant | 31/36 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00149 AC: 226AN: 152188Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00145 AC: 364AN: 251048Hom.: 0 AF XY: 0.00150 AC XY: 203AN XY: 135774
GnomAD4 exome AF: 0.00214 AC: 3132AN: 1461812Hom.: 6 Cov.: 32 AF XY: 0.00203 AC XY: 1474AN XY: 727206
GnomAD4 genome ? AF: 0.00148 AC: 226AN: 152306Hom.: 0 Cov.: 33 AF XY: 0.00122 AC XY: 91AN XY: 74460
ClinVar
Submissions by phenotype
Weill-Marchesani syndrome Uncertain:1
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Weill-Marchesani syndrome 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Aug 01, 2017 | LTBP2 NM_000428.2 exon31 p.Val1506Met (c.4516G>A): This variant has not been reported in the literature but is present in 0.2% (245/126544) of European chromosomes in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs117800773). This variant is present in ClinVar (Variation ID:314272). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Glaucoma 3, primary congenital, D Uncertain:1
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Glaucoma 3, primary congenital, D;C3538951:Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma;C3553785:Weill-Marchesani syndrome 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | LTBP2 NM_000428.2 exon31 p.Val1506Met (c.4516G>A): This variant has not been reported in the literature but is present in 0.2% (245/126544) of European chromosomes in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs117800773). This variant is present in ClinVar (Variation ID:314272). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
LTBP2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 09, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at