Variant rs554570575 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The NM_000428.3(LTBP2):c.804_821delGCCCGCACCACAGTCGCC(p.Pro269_Pro274del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,613,680 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

LTBP2
NM_000428.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 1.65

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_000428.3.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTBP2	NM_000428.3 link	c.804_821delGCCCGCACCACAGTCGCC	p.Pro269_Pro274del	disruptive_inframe_deletion	3/36	ENST00000261978.9	NP_000419.1	Q14767

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LTBP2	ENST00000261978.9 link	c.804_821delGCCCGCACCACAGTCGCC	p.Pro269_Pro274del	disruptive_inframe_deletion	3/36	1	NM_000428.3	ENSP00000261978.4	Q14767
LTBP2	ENST00000556690.5 link	c.804_821delGCCCGCACCACAGTCGCC	p.Pro269_Pro274del	disruptive_inframe_deletion	3/35	5		ENSP00000451477.1	G3V3X5
LTBP2	ENST00000553939.5 link	n.804_821delGCCCGCACCACAGTCGCC		non_coding_transcript_exon_variant	3/36	5		ENSP00000452110.1	G3V511
LTBP2	ENST00000557425.1 link	n.123+26166_123+26183delGCCCGCACCACAGTCGCC		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000224

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000181

AC:

AN:

249146

Hom.:

AF XY:

0.000185

AC XY:

AN XY:

134872

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.0000289

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:

0.000376

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000205

AC:

299

AN:

1461604

Hom.:

AF XY:

0.000206

AC XY:

150

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000250

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000224

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000131

Hom.:

Bravo

AF:

0.000310

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Weill-Marchesani syndrome 3

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

3billion

May 22, 2022

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.016%). Inframe deletion located in a nonrepeat region: predicted to change the length of the protein and disrupt normal protein function. Therefore, this variant is classified as uncertain significanceaccording to the recommendation of ACMG/AMP guideline. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 30, 2022

This variant, c.804_821del, results in the deletion of 6 amino acid(s) of the LTBP2 protein (p.Pro271_Ala276del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs757670961, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with LTBP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1365526). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

LTBP2-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 09, 2024

The LTBP2 c.804_821del18 variant is predicted to result in an in-frame deletion (p.Pro271_Ala276del). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.034% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over