14-74512162-C-T

Variant names:

• chr14-74512162-C-T
• rs862057
• NM_000428.3:c.2909-798G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000428.3(LTBP2):​c.2909-798G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,028 control chromosomes in the GnomAD database, including 30,978 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (30978 hom., cov: 32)
• Consequence: LTBP2 NM_000428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• glaucoma 3, primary congenital, D

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• Weill-Marchesani syndrome 3

  Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• congenital glaucoma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Weill-Marchesani syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• glaucoma secondary to spherophakia/ectopia lentis and megalocornea

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP2	NM_000428.3	c.2909-798G>A		intron_variant	Intron 18 of 35	ENST00000261978.9	NP_000419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP2	ENST00000261978.9	c.2909-798G>A		intron_variant	Intron 18 of 35	1	NM_000428.3	ENSP00000261978.4
LTBP2	ENST00000556690.5	c.2909-798G>A		intron_variant	Intron 18 of 34	5		ENSP00000451477.1
LTBP2	ENST00000553939.5	n.2909-798G>A		intron_variant	Intron 18 of 35	5		ENSP00000452110.1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96747 AN: 151912 Hom.: 30952 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.636

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.637 AC: 96824 AN: 152028 Hom.: 30978 Cov.: 32 AF XY: 0.636 AC XY: 47256 AN XY: 74292

African (AFR) AF: 0.598 AC: 24780 AN: 41468

American (AMR) AF: 0.643 AC: 9839 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2154 AN: 3466

East Asian (EAS) AF: 0.746 AC: 3840 AN: 5148

South Asian (SAS) AF: 0.624 AC: 3005 AN: 4812

European-Finnish (FIN) AF: 0.677 AC: 7162 AN: 10576

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.647 AC: 43971 AN: 67954

Other (OTH) AF: 0.635 AC: 1340 AN: 2110

Alfa AF: 0.642 Hom.: 96927

Bravo AF: 0.637

Asia WGS AF: 0.672 AC: 2339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.0
DANN	Benign	0.81
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs862057; hg19: chr14-74978865;