Genetic Variant NM_000428.3:c.*1777A>G (chr14-74499107-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000428.3(LTBP2):c.*1777A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 65,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

LTBP2
NM_000428.3 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: -0.646

Publications

0 publications found

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 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

LTBP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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.*1777A>G		3_prime_UTR	Exon 36 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.*1777A>G		3_prime_UTR	Exon 36 of 36	ENSP00000261978.4	Q14767
	LTBP2	ENST00000945197.1		c.*1777A>G		3_prime_UTR	Exon 35 of 35	ENSP00000615256.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.000138

AC:

AN:

65352

Hom.:

Cov.:

AF XY:

0.000132

AC XY:

AN XY:

30298

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

3076

American (AMR)

AF:

0.00

AC:

AN:

1934

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4090

East Asian (EAS)

AF:

0.000954

AC:

AN:

9436

South Asian (SAS)

AF:

0.00

AC:

AN:

578

European-Finnish (FIN)

AF:

0.00

AC:

AN:

158

Middle Eastern (MID)

AF:

0.00

AC:

AN:

410

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

40260

Other (OTH)

AF:

0.00

AC:

AN:

5410

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Glaucoma 3, primary congenital, D (1)

Weill-Marchesani syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.57

(source)

DANN

Benign

0.78

PhyloP100

-0.65

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over