chr2-169156300-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2
The NM_004525.3(LRP2):c.12125G>A(p.Arg4042His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00051 in 1,613,718 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R4042C) has been classified as Uncertain significance.
Frequency
Consequence
NM_004525.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRP2 | NM_004525.3 | c.12125G>A | p.Arg4042His | missense_variant | 65/79 | ENST00000649046.1 | |
LRP2 | XM_011511183.4 | c.11996G>A | p.Arg3999His | missense_variant | 64/78 | ||
LRP2 | XM_047444340.1 | c.11201G>A | p.Arg3734His | missense_variant | 65/79 | ||
LRP2 | XM_011511184.3 | c.9836G>A | p.Arg3279His | missense_variant | 50/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRP2 | ENST00000649046.1 | c.12125G>A | p.Arg4042His | missense_variant | 65/79 | NM_004525.3 | P1 | ||
LRP2 | ENST00000649153.1 | c.3026G>A | p.Arg1009His | missense_variant, NMD_transcript_variant | 17/30 | ||||
LRP2 | ENST00000650252.1 | c.1157G>A | p.Arg386His | missense_variant, NMD_transcript_variant | 10/24 |
Frequencies
GnomAD3 genomes AF: 0.000362 AC: 55AN: 152136Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00110 AC: 277AN: 251398Hom.: 6 AF XY: 0.00139 AC XY: 189AN XY: 135872
GnomAD4 exome AF: 0.000526 AC: 768AN: 1461464Hom.: 10 Cov.: 31 AF XY: 0.000723 AC XY: 526AN XY: 727050
GnomAD4 genome AF: 0.000361 AC: 55AN: 152254Hom.: 0 Cov.: 32 AF XY: 0.000443 AC XY: 33AN XY: 74448
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 25, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2023 | LRP2: BP4, BS2 - |
Donnai-Barrow syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at