rs699374

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000428.3(LTBP2):c.2406T>C(p.Thr802Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,602,476 control chromosomes in the GnomAD database, including 73,196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10297 hom., cov: 32)

Exomes 𝑓: 0.29 ( 62899 hom. )

Consequence

LTBP2
NM_000428.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.245

Publications

22 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: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 14-74526097-A-G is Benign according to our data. Variant chr14-74526097-A-G is described in ClinVar as Benign. ClinVar VariationId is 256097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.245 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

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.2406T>C	p.Thr802Thr	synonymous	Exon 14 of 36	NP_000419.1	Q14767

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LTBP2	ENST00000261978.9	TSL:1 MANE Select	c.2406T>C	p.Thr802Thr	synonymous	Exon 14 of 36	ENSP00000261978.4	Q14767
LTBP2	ENST00000945197.1		c.2406T>C	p.Thr802Thr	synonymous	Exon 14 of 35	ENSP00000615256.1
LTBP2	ENST00000556690.5	TSL:5	c.2406T>C	p.Thr802Thr	synonymous	Exon 14 of 35	ENSP00000451477.1	G3V3X5

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53535

AN:

151888

Hom.:

10270

Cov.:

show subpopulations

Gnomad AFR

AF:

0.501

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.389

Gnomad ASJ

AF:

0.262

Gnomad EAS

AF:

0.338

Gnomad SAS

AF:

0.286

Gnomad FIN

AF:

0.278

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.278

Gnomad OTH

AF:

0.330

GnomAD2 exomes

AF:

0.305

AC:

70676

AN:

231634

AF XY:

0.295

show subpopulations

Gnomad AFR exome

AF:

0.494

Gnomad AMR exome

AF:

0.410

Gnomad ASJ exome

AF:

0.257

Gnomad EAS exome

AF:

0.339

Gnomad FIN exome

AF:

0.270

Gnomad NFE exome

AF:

0.263

Gnomad OTH exome

AF:

0.299

GnomAD4 exome

AF:

0.291

AC:

421557

AN:

1450470

Hom.:

62899

Cov.:

AF XY:

0.288

AC XY:

207418

AN XY:

720338

show subpopulations

African (AFR)

AF:

0.512

AC:

17022

AN:

33270

American (AMR)

AF:

0.407

AC:

17617

AN:

43290

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

6803

AN:

25894

East Asian (EAS)

AF:

0.337

AC:

13253

AN:

39328

South Asian (SAS)

AF:

0.269

AC:

22694

AN:

84340

European-Finnish (FIN)

AF:

0.279

AC:

14680

AN:

52640

Middle Eastern (MID)

AF:

0.299

AC:

1705

AN:

5710

European-Non Finnish (NFE)

AF:

0.280

AC:

309838

AN:

1106014

Other (OTH)

AF:

0.299

AC:

17945

AN:

59984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

16230

32460

48690

64920

81150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10558

21116

31674

42232

52790

<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

AF:

0.353

AC:

53605

AN:

152006

Hom.:

10297

Cov.:

AF XY:

0.351

AC XY:

26061

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.501

AC:

20770

AN:

41424

American (AMR)

AF:

0.390

AC:

5956

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.262

AC:

911

AN:

3472

East Asian (EAS)

AF:

0.338

AC:

1747

AN:

5166

South Asian (SAS)

AF:

0.286

AC:

1381

AN:

4824

European-Finnish (FIN)

AF:

0.278

AC:

2940

AN:

10574

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.278

AC:

18916

AN:

67950

Other (OTH)

AF:

0.331

AC:

700

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1699

3399

5098

6798

8497

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

508

1016

1524

2032

2540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.302

Hom.:

28539

Bravo

AF:

0.372

Asia WGS

AF:

0.337

AC:

1171

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (3)

Glaucoma 3, primary congenital, D (1)

Microspherophakia (1)

Weill-Marchesani syndrome (1)

Weill-Marchesani syndrome 3 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

5.4

(source)

DANN

Benign

0.32

PhyloP100

0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over