rs1555172311

Positions:

• chr11-46877220-TG-GT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002334.4(LRP4):​c.3255_3256delCAinsAC​(p.Ile1086Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: LRP4 NM_002334.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13

Genes affected

LRP4 (HGNC:6696): (LDL receptor related protein 4) This gene encodes a member of the low-density lipoprotein receptor-related protein family. The encoded protein may be a regulator of Wnt signaling. Mutations in this gene are associated with Cenani-Lenz syndrome. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP4	NM_002334.4	c.3255_3256delCAinsAC	p.Ile1086Leu	missense_variant		ENST00000378623.6	NP_002325.2
LRP4	XM_017017734.2	c.3255_3256delCAinsAC	p.Ile1086Leu	missense_variant			XP_016873223.1
LRP4	XM_011520103.3	c.2451_2452delCAinsAC	p.Ile818Leu	missense_variant			XP_011518405.1
LRP4	XM_011520104.3	c.1020_1021delCAinsAC	p.Ile341Leu	missense_variant			XP_011518406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP4	ENST00000378623.6	c.3255_3256delCAinsAC	p.Ile1086Leu	missense_variant		1	NM_002334.4	ENSP00000367888.1

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cenani-Lenz syndactyly syndrome;C3280402:Sclerosteosis 2;C4225377:Congenital myasthenic syndrome 17 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 09, 2021

This sequence change replaces isoleucine with valine at codon 1086 of the LRP4 protein (p.Ile1086Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. The frequency data for this variant in the population databases is not available, as this variant may be reported as separate entries in the ExAC database. This variant has not been reported in the literature in individuals with LRP4-related conditions. 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. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1555172311; hg19: chr11-46898771;