14-74552299-C-A

Variant names:

• chr14-74552299-C-A
• NM_000428.3:c.1287G>T
• LTBP2 p.Leu429Leu

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_000428.3(LTBP2):​c.1287G>T​(p.Leu429Leu) variant causes a synonymous 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. Variant has been reported in ClinVar as (no stars). Synonymous variant affecting the same amino acid position (i.e. L429L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LTBP2 NM_000428.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.751
• Publications: 0 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Weill-Marchesani syndrome 3

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

ENSG00000258425 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP7: Synonymous conserved (PhyloP=0.751 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000428.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTBP2	NM_000428.3	MANE Select	c.1287G>T	p.Leu429Leu	synonymous	Exon 6 of 36	NP_000419.1	Q14767

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTBP2	ENST00000261978.9	TSL:1 MANE Select	c.1287G>T	p.Leu429Leu	synonymous	Exon 6 of 36	ENSP00000261978.4	Q14767
	LTBP2	ENST00000945197.1		c.1287G>T	p.Leu429Leu	synonymous	Exon 6 of 35	ENSP00000615256.1
	LTBP2	ENST00000556690.5	TSL:5	c.1287G>T	p.Leu429Leu	synonymous	Exon 6 of 35	ENSP00000451477.1	G3V3X5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	17
DANN	Benign	0.94
PhyloP100		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-75019002;