Variant 11-68312746-CGCTGCT-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6

The NM_002335.4(LRP5):c.55_60del(p.Leu19_Leu20del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000307 in 1,060,390 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

LRP5
NM_002335.4 inframe_deletion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 0.00

Variant links:

Genes affected

LRP5 (HGNC:6697): (LDL receptor related protein 5) This gene encodes a transmembrane low-density lipoprotein receptor that binds and internalizes ligands in the process of receptor-mediated endocytosis. This protein also acts as a co-receptor with Frizzled protein family members for transducing signals by Wnt proteins and was originally cloned on the basis of its association with type 1 diabetes mellitus in humans. This protein plays a key role in skeletal homeostasis and many bone density related diseases are caused by mutations in this gene. Mutations in this gene also cause familial exudative vitreoretinopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

LRP5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 11-68312746-CGCTGCT-C is Benign according to our data. Variant chr11-68312746-CGCTGCT-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 286883.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2}. Variant chr11-68312746-CGCTGCT-C is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP5	NM_002335.4 linkuse as main transcript	c.55_60del	p.Leu19_Leu20del	inframe_deletion	1/23	ENST00000294304.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP5	ENST00000294304.12 linkuse as main transcript	c.55_60del	p.Leu19_Leu20del	inframe_deletion	1/23	1	NM_002335.4	P1
LRP5	ENST00000529993.5 linkuse as main transcript	c.55_60del	p.Leu19_Leu20del	inframe_deletion, NMD_transcript_variant	1/23	1

Frequencies

GnomAD3 genomes

AF:

0.000270

AC:

AN:

144332

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000137

Gnomad ASJ

AF:

0.000297

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000211

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00671

Gnomad NFE

AF:

0.000307

Gnomad OTH

AF:

0.00150

GnomAD4 exome

AF:

0.000313

AC:

287

AN:

915972

Hom.:

AF XY:

0.000327

AC XY:

143

AN XY:

437958

show subpopulations

Gnomad4 AFR exome

AF:

0.000118

Gnomad4 AMR exome

AF:

0.00106

Gnomad4 ASJ exome

AF:

0.000864

Gnomad4 EAS exome

AF:

0.000858

Gnomad4 SAS exome

AF:

0.000801

Gnomad4 FIN exome

AF:

0.000512

Gnomad4 NFE exome

AF:

0.000276

Gnomad4 OTH exome

AF:

0.000384

GnomAD4 genome

AF:

0.000270

AC:

AN:

144418

Hom.:

Cov.:

AF XY:

0.000213

AC XY:

AN XY:

70314

show subpopulations

Gnomad4 AFR

AF:

0.000250

Gnomad4 AMR

AF:

0.000136

Gnomad4 ASJ

AF:

0.000297

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000211

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000307

Gnomad4 OTH

AF:

0.00149

Bravo

AF:

0.000378

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 31, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Osteogenesis imperfecta

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Oct 21, 2021

- -

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