rs587780382
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004525.3(LRP2):c.7384_7390+8dupGCTTCAGGTAAGTGC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000211 in 1,613,552 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_004525.3 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LRP2 | NM_004525.3 | c.7384_7390+8dupGCTTCAGGTAAGTGC | splice_region_variant, intron_variant | Intron 39 of 78 | ENST00000649046.1 | NP_004516.2 | ||
LRP2 | XM_011511183.4 | c.7384_7390+8dupGCTTCAGGTAAGTGC | splice_region_variant, intron_variant | Intron 39 of 77 | XP_011509485.1 | |||
LRP2 | XM_047444340.1 | c.6460_6466+8dupGCTTCAGGTAAGTGC | splice_region_variant, intron_variant | Intron 39 of 78 | XP_047300296.1 | |||
LRP2 | XM_011511184.3 | c.5095_5101+8dupGCTTCAGGTAAGTGC | splice_region_variant, intron_variant | Intron 24 of 63 | XP_011509486.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000210 AC: 32AN: 152088Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000112 AC: 28AN: 250750Hom.: 0 AF XY: 0.0000959 AC XY: 13AN XY: 135542
GnomAD4 exome AF: 0.000211 AC: 309AN: 1461464Hom.: 0 Cov.: 33 AF XY: 0.000205 AC XY: 149AN XY: 727044
GnomAD4 genome AF: 0.000210 AC: 32AN: 152088Hom.: 0 Cov.: 32 AF XY: 0.000162 AC XY: 12AN XY: 74280
ClinVar
Submissions by phenotype
Donnai-Barrow syndrome Uncertain:2
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not provided Uncertain:2
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This sequence change falls in intron 39 of the LRP2 gene. It does not directly change the encoded amino acid sequence of the LRP2 protein. This variant is present in population databases (rs587780382, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with LRP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 129489). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. -
Congenital heart disease Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at