14-74552299-C-T

Position:

chr14-74552299-C-T

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.751

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:

(HGNC:):

links:

Genome browser will be placed here

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 linkuse as main transcript	c.1287G>A	p.Leu429=	synonymous_variant	6/36	ENST00000261978.9	NP_000419.1
LOC124903346	XR_007064265.1 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTBP2	ENST00000261978.9 linkuse as main transcript	c.1287G>A	p.Leu429=	synonymous_variant	6/36	1	NM_000428.3	ENSP00000261978	P1
	ENST00000554552.1 linkuse as main transcript	n.119C>T		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

AF:

0.0638

AC:

9704

AN:

152168

Hom.:

340

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0837

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0677

Gnomad ASJ

AF:

0.0937

Gnomad EAS

AF:

0.0801

Gnomad SAS

AF:

0.0447

Gnomad FIN

AF:

0.0520

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0516

Gnomad OTH

AF:

0.0702

GnomAD3 exomes

AF:

0.0597

AC:

14854

AN:

249004

Hom.:

454

AF XY:

0.0587

AC XY:

7932

AN XY:

135018

show subpopulations

Gnomad AFR exome

AF:

0.0874

Gnomad AMR exome

AF:

0.0584

Gnomad ASJ exome

AF:

0.0753

Gnomad EAS exome

AF:

0.0862

Gnomad SAS exome

AF:

0.0526

Gnomad FIN exome

AF:

0.0566

Gnomad NFE exome

AF:

0.0527

Gnomad OTH exome

AF:

0.0616

GnomAD4 exome

AF:

0.0552

AC:

80634

AN:

1460900

Hom.:

2403

Cov.:

AF XY:

0.0553

AC XY:

40204

AN XY:

726762

show subpopulations

Gnomad4 AFR exome

AF:

0.0847

Gnomad4 AMR exome

AF:

0.0608

Gnomad4 ASJ exome

AF:

0.0796

Gnomad4 EAS exome

AF:

0.0963

Gnomad4 SAS exome

AF:

0.0528

Gnomad4 FIN exome

AF:

0.0565

Gnomad4 NFE exome

AF:

0.0519

Gnomad4 OTH exome

AF:

0.0569

GnomAD4 genome

AF:

0.0637

AC:

9702

AN:

152286

Hom.:

339

Cov.:

AF XY:

0.0636

AC XY:

4734

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0835

Gnomad4 AMR

AF:

0.0676

Gnomad4 ASJ

AF:

0.0937

Gnomad4 EAS

AF:

0.0803

Gnomad4 SAS

AF:

0.0448

Gnomad4 FIN

AF:

0.0520

Gnomad4 NFE

AF:

0.0516

Gnomad4 OTH

AF:

0.0695

Alfa

AF:

0.0591

Hom.:

161

Bravo

AF:

0.0671

Asia WGS

AF:

0.0690

AC:

239

AN:

3478

EpiCase

AF:

0.0556

EpiControl

AF:

0.0573

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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