rs4667596
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1
The NM_004525.3(LRP2):c.6035G>A(p.Arg2012Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0211 in 1,611,600 control chromosomes in the GnomAD database, including 650 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 Benign (★★).
Frequency
Consequence
NM_004525.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRP2 | NM_004525.3 | c.6035G>A | p.Arg2012Lys | missense_variant | 36/79 | ENST00000649046.1 | |
LRP2 | XM_011511183.4 | c.6035G>A | p.Arg2012Lys | missense_variant | 36/78 | ||
LRP2 | XM_047444340.1 | c.5111G>A | p.Arg1704Lys | missense_variant | 36/79 | ||
LRP2 | XM_011511184.3 | c.3746G>A | p.Arg1249Lys | missense_variant | 21/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRP2 | ENST00000649046.1 | c.6035G>A | p.Arg2012Lys | missense_variant | 36/79 | NM_004525.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0183 AC: 2785AN: 152140Hom.: 65 Cov.: 32
GnomAD3 exomes AF: 0.0264 AC: 6577AN: 248814Hom.: 196 AF XY: 0.0235 AC XY: 3169AN XY: 134672
GnomAD4 exome AF: 0.0214 AC: 31238AN: 1459340Hom.: 584 Cov.: 31 AF XY: 0.0206 AC XY: 14988AN XY: 726136
GnomAD4 genome ? AF: 0.0183 AC: 2792AN: 152260Hom.: 66 Cov.: 32 AF XY: 0.0184 AC XY: 1367AN XY: 74444
ClinVar
Submissions by phenotype
Donnai-Barrow syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at