rs78258030

Positions:

chr14-74521898-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000428.3(LTBP2):c.2788+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 1,613,784 control chromosomes in the GnomAD database, including 823 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 184 hom., cov: 33)

Exomes 𝑓: 0.019 ( 639 hom. )

Consequence

LTBP2
NM_000428.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.69

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]

LTBP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 14-74521898-G-A is Benign according to our data. Variant chr14-74521898-G-A is described in ClinVar as [Benign]. Clinvar id is 256098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-74521898-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTBP2	NM_000428.3 linkuse as main transcript	c.2788+13C>T		intron_variant		ENST00000261978.9	NP_000419.1	Q14767

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
LTBP2	ENST00000261978.9 linkuse as main transcript	c.2788+13C>T	intron_variant	1	NM_000428.3	ENSP00000261978.4	Q14767
LTBP2	ENST00000556690.5 linkuse as main transcript	c.2788+13C>T	intron_variant	5		ENSP00000451477.1	G3V3X5
LTBP2	ENST00000553939.5 linkuse as main transcript	n.2788+13C>T	intron_variant	5		ENSP00000452110.1	G3V511

Frequencies

GnomAD3 genomes

AF:

0.0350

AC:

5323

AN:

152194

Hom.:

185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0841

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0196

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.0821

Gnomad FIN

AF:

0.00791

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0141

Gnomad OTH

AF:

0.0268

GnomAD3 exomes

AF:

0.0246

AC:

6182

AN:

251064

Hom.:

195

AF XY:

0.0269

AC XY:

3658

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.0866

Gnomad AMR exome

AF:

0.00995

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.00147

Gnomad SAS exome

AF:

0.0828

Gnomad FIN exome

AF:

0.00783

Gnomad NFE exome

AF:

0.0139

Gnomad OTH exome

AF:

0.0157

GnomAD4 exome

AF:

0.0187

AC:

27365

AN:

1461474

Hom.:

639

Cov.:

AF XY:

0.0205

AC XY:

14902

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.0858

Gnomad4 AMR exome

AF:

0.0107

Gnomad4 ASJ exome

AF:

0.00272

Gnomad4 EAS exome

AF:

0.000756

Gnomad4 SAS exome

AF:

0.0823

Gnomad4 FIN exome

AF:

0.00813

Gnomad4 NFE exome

AF:

0.0135

Gnomad4 OTH exome

AF:

0.0198

GnomAD4 genome

AF:

0.0349

AC:

5316

AN:

152310

Hom.:

184

Cov.:

AF XY:

0.0348

AC XY:

2591

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0838

Gnomad4 AMR

AF:

0.0195

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00232

Gnomad4 SAS

AF:

0.0815

Gnomad4 FIN

AF:

0.00791

Gnomad4 NFE

AF:

0.0141

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.0247

Hom.:

Bravo

AF:

0.0354

Asia WGS

AF:

0.0460

AC:

161

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 08, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.0050

DANN

Benign

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over