2-169204093-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_004525.3(LRP2):āc.7894A>Cā(p.Asn2632His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N2632D) has been classified as Benign.
Frequency
Consequence
NM_004525.3 missense
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRP2 | NM_004525.3 | c.7894A>C | p.Asn2632His | missense_variant | 42/79 | ENST00000649046.1 | |
LRP2 | XM_011511183.4 | c.7894A>C | p.Asn2632His | missense_variant | 42/78 | ||
LRP2 | XM_047444340.1 | c.6970A>C | p.Asn2324His | missense_variant | 42/79 | ||
LRP2 | XM_011511184.3 | c.5605A>C | p.Asn1869His | missense_variant | 27/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRP2 | ENST00000649046.1 | c.7894A>C | p.Asn2632His | missense_variant | 42/79 | NM_004525.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152150Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251404Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135860
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461884Hom.: 0 Cov.: 33 AF XY: 0.00000825 AC XY: 6AN XY: 727248
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152150Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74328
ClinVar
Submissions by phenotype
Donnai-Barrow syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 23, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2022 | This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 2632 of the LRP2 protein (p.Asn2632His). This variant is present in population databases (rs17848169, gnomAD 0.0009%). 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: 894706). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LRP2 protein function. 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at