14-74526070-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_000428.3(LTBP2):​c.2428+5G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Consequence

LTBP2
NM_000428.3 splice_region, intron

Scores

2
Splicing: ADA: 0.9992
2

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 2.16
Variant links:
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 Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 14-74526070-C-G is Pathogenic according to our data. Variant chr14-74526070-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 191286.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LTBP2NM_000428.3 linkc.2428+5G>C splice_region_variant, intron_variant ENST00000261978.9 NP_000419.1 Q14767

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LTBP2ENST00000261978.9 linkc.2428+5G>C splice_region_variant, intron_variant 1 NM_000428.3 ENSP00000261978.4 Q14767
LTBP2ENST00000556690.5 linkc.2428+5G>C splice_region_variant, intron_variant 5 ENSP00000451477.1 G3V3X5
LTBP2ENST00000553939.5 linkn.2428+5G>C splice_region_variant, intron_variant 5 ENSP00000452110.1 G3V511

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitterresearchCenter for Genomic Medicine, King Faisal Specialist Hospital and Research Center-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.31
CADD
Benign
21
DANN
Benign
0.87

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.92
SpliceAI score (max)
0.56
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.56
Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs786205624; hg19: chr14-74992773; API