rs2079631
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_000428.3(LTBP2):c.4782G>A(p.Val1594=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00381 in 1,613,964 control chromosomes in the GnomAD database, including 228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.020 ( 104 hom., cov: 33)
Exomes 𝑓: 0.0021 ( 124 hom. )
Consequence
LTBP2
NM_000428.3 synonymous
NM_000428.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.679
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
Variant 14-74503325-C-T is Benign according to our data. Variant chr14-74503325-C-T is described in ClinVar as [Benign]. Clinvar id is 256099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-74503325-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.679 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0682 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LTBP2 | NM_000428.3 | c.4782G>A | p.Val1594= | synonymous_variant | 33/36 | ENST00000261978.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LTBP2 | ENST00000261978.9 | c.4782G>A | p.Val1594= | synonymous_variant | 33/36 | 1 | NM_000428.3 | P1 | |
LTBP2 | ENST00000556690.5 | c.4650G>A | p.Val1550= | synonymous_variant | 32/35 | 5 | |||
LTBP2 | ENST00000553939.5 | c.4782G>A | p.Val1594= | synonymous_variant, NMD_transcript_variant | 33/36 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0199 AC: 3028AN: 152244Hom.: 103 Cov.: 33
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GnomAD3 exomes AF: 0.00512 AC: 1283AN: 250594Hom.: 48 AF XY: 0.00367 AC XY: 498AN XY: 135546
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GnomAD4 exome AF: 0.00212 AC: 3105AN: 1461602Hom.: 124 Cov.: 32 AF XY: 0.00181 AC XY: 1316AN XY: 727132
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GnomAD4 genome ? AF: 0.0200 AC: 3041AN: 152362Hom.: 104 Cov.: 33 AF XY: 0.0194 AC XY: 1446AN XY: 74510
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 08, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
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 12, 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 12, 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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Name
Calibrated prediction
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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