2-169127533-TAAAAAAAA-TAAAAAAAAAAAA

Variant names:

• chr2-169127533-T-TAAAA
• rs3083240
• NM_004525.3:c.*1126_*1129dupTTTT

Variant summary

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

The NM_004525.3(LRP2):​c.*1126_*1129dupTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.033 (84 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRP2 NM_004525.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518

Genes affected

LRP2 (HGNC:6694): (LDL receptor related protein 2) The protein encoded by this gene, low density lipoprotein-related protein 2 (LRP2) or megalin, is a multi-ligand endocytic receptor that is expressed in many different tissues but primarily in absorptive epithilial tissues such as the kidney. This glycoprotein has a large amino-terminal extracellular domain, a single transmembrane domain, and a short carboxy-terminal cytoplasmic tail. The extracellular ligand-binding-domains bind diverse macromolecules including albumin, apolipoproteins B and E, and lipoprotein lipase. The LRP2 protein is critical for the reuptake of numerous ligands, including lipoproteins, sterols, vitamin-binding proteins, and hormones. This protein also has a role in cell-signaling; extracellular ligands include parathyroid horomones and the morphogen sonic hedgehog while cytosolic ligands include MAP kinase scaffold proteins and JNK interacting proteins. Recycling of this membrane receptor is regulated by phosphorylation of its cytoplasmic domain. Mutations in this gene cause Donnai-Barrow syndrome (DBS) and facio-oculoacoustico-renal syndrome (FOAR).[provided by RefSeq, Aug 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP2	NM_004525.3	c.*1126_*1129dupTTTT		3_prime_UTR_variant	Exon 79 of 79	ENST00000649046.1	NP_004516.2
LRP2	XM_011511183.4	c.*1126_*1129dupTTTT		3_prime_UTR_variant	Exon 78 of 78		XP_011509485.1
LRP2	XM_047444340.1	c.*1126_*1129dupTTTT		3_prime_UTR_variant	Exon 79 of 79		XP_047300296.1
LRP2	XM_011511184.3	c.*1126_*1129dupTTTT		3_prime_UTR_variant	Exon 64 of 64		XP_011509486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP2	ENST00000649046	c.*1126_*1129dupTTTT		3_prime_UTR_variant	Exon 79 of 79		NM_004525.3	ENSP00000496870.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2122 AN: 64426 Hom.: 84 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0748

Gnomad AMI AF: 0.00667

Gnomad AMR AF: 0.0236

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.00223

Gnomad SAS AF: 0.0335

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.0300

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.0192

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 126 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 72

Gnomad4 FIN exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0329 AC: 2121 AN: 64416 Hom.: 84 Cov.: 0 AF XY: 0.0326 AC XY: 917 AN XY: 28170

Gnomad4 AFR AF: 0.0747

Gnomad4 AMR AF: 0.0236

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.00224

Gnomad4 SAS AF: 0.0338

Gnomad4 FIN AF: 0.0193

Gnomad4 NFE AF: 0.0221

Gnomad4 OTH AF: 0.0191

ClinVar

Not reported in ClinVar

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: rs3083240; hg19: chr2-169984043;