Variant rs137854856 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2PM5BP4_Moderate

The NM_000428.3(LTBP2):c.3529G>C(p.Val1177Leu) variant causes a missense, splice region 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. 16/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1177M) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 33)

Consequence

LTBP2
NM_000428.3 missense, splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.453

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr14-74508727-C-T is described in Lovd as [Pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.14197922).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTBP2	NM_000428.3 linkuse as main transcript	c.3529G>C	p.Val1177Leu	missense_variant, splice_region_variant	24/36	ENST00000261978.9	NP_000419.1	Q14767

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LTBP2	ENST00000261978.9 linkuse as main transcript	c.3529G>C	p.Val1177Leu	missense_variant, splice_region_variant	24/36	1	NM_000428.3	ENSP00000261978.4	Q14767
LTBP2	ENST00000556690.5 linkuse as main transcript	c.3529G>C	p.Val1177Leu	missense_variant, splice_region_variant	24/35	5		ENSP00000451477.1	G3V3X5
LTBP2	ENST00000556206.1 linkuse as main transcript	c.325G>C	p.Val109Leu	missense_variant, splice_region_variant	4/6	5		ENSP00000450668.1	H0YJ20
LTBP2	ENST00000553939.5 linkuse as main transcript	n.3529G>C		splice_region_variant, non_coding_transcript_exon_variant	24/36	5		ENSP00000452110.1	G3V511

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251088

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.035

BayesDel_noAF

Benign

-0.29

CADD

Benign

9.4

DANN

Benign

0.79

DEOGEN2

Uncertain

0.46

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.050

MetaRNN

Benign

0.14

T;T

MetaSVM

Uncertain

-0.16

MutationAssessor

Benign

1.2

L;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.16

Sift

Uncertain

0.012

D;D

Sift4G

Benign

0.18

T;T

Polyphen

0.053

B;.

Vest4

0.21

MutPred

0.65

Gain of catalytic residue at M1181 (P = 0.0077);Gain of catalytic residue at M1181 (P = 0.0077);

MVP

0.43

MPC

0.14

ClinPred

0.065

GERP RS

-1.3

Varity_R

0.22

gMVP

0.20

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over