rs61738025
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_000428.3(LTBP2):c.1287G>A(p.Leu429=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.056 in 1,613,186 control chromosomes in the GnomAD database, including 2,742 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.064 ( 339 hom., cov: 32)
Exomes 𝑓: 0.055 ( 2403 hom. )
Consequence
LTBP2
NM_000428.3 synonymous
NM_000428.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.751
Genes affected
LTBP2 (HGNC:6715): (latent transforming growth factor beta binding protein 2) The protein encoded by this gene belongs to the family of latent transforming growth factor (TGF)-beta binding proteins (LTBP), which are extracellular matrix proteins with multi-domain structure. This protein is the largest member of the LTBP family possessing unique regions and with most similarity to the fibrillins. It has thus been suggested that it may have multiple functions: as a member of the TGF-beta latent complex, as a structural component of microfibrils, and a role in cell adhesion. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BP6
Variant 14-74552299-C-T is Benign according to our data. Variant chr14-74552299-C-T is described in ClinVar as [Benign]. Clinvar id is 256096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-74552299-C-T is described in Lovd as [Benign]. Variant chr14-74552299-C-T is described in Lovd as [Likely_benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0812 is higher than 0.05.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| LTBP2 | NM_000428.3 | c.1287G>A | p.Leu429= | synonymous_variant | 6/36 | ENST00000261978.9 | NP_000419.1 | |
| LOC124903346 | XR_007064265.1 | upstream_gene_variant |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| LTBP2 | ENST00000261978.9 | c.1287G>A | p.Leu429= | synonymous_variant | 6/36 | 1 | NM_000428.3 | ENSP00000261978 | P1 | |
| ENST00000554552.1 | n.119C>T | non_coding_transcript_exon_variant | 1/2 | 4 |
Frequencies
GnomAD3 genomes 0.0638 AC: 9704AN: 152168Hom.: 340 Cov.: 32
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GnomAD3 exomes AF: 0.0597 AC: 14854AN: 249004Hom.: 454 AF XY: 0.0587 AC XY: 7932AN XY: 135018
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GnomAD4 exome AF: 0.0552 AC: 80634AN: 1460900Hom.: 2403 Cov.: 38 AF XY: 0.0553 AC XY: 40204AN XY: 726762
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GnomAD4 genome 0.0637 AC: 9702AN: 152286Hom.: 339 Cov.: 32 AF XY: 0.0636 AC XY: 4734AN XY: 74474
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
| Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
| Benign, criteria provided, single submitter | clinical testing | GeneDx | May 01, 2018 | 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. - |
| Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
| Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Weill-Marchesani syndrome Benign:1
| 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. - |
Glaucoma 3, primary congenital, D Benign:1
| 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. - |
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