chr3-49124751-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_002292.4(LAMB2):c.3059C>A(p.Ala1020Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002292.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMB2 | NM_002292.4 | c.3059C>A | p.Ala1020Asp | missense_variant | 21/32 | ENST00000305544.9 | |
LAMB2 | XM_005265127.5 | c.3059C>A | p.Ala1020Asp | missense_variant | 22/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMB2 | ENST00000305544.9 | c.3059C>A | p.Ala1020Asp | missense_variant | 21/32 | 1 | NM_002292.4 | P1 | |
LAMB2 | ENST00000418109.5 | c.3059C>A | p.Ala1020Asp | missense_variant | 22/33 | 1 | P1 | ||
LAMB2 | ENST00000462930.5 | n.466C>A | non_coding_transcript_exon_variant | 3/3 | 2 | ||||
LAMB2 | ENST00000542580.1 | n.374C>A | non_coding_transcript_exon_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461844Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 727218
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Pierson syndrome;C3280113:LAMB2-related infantile-onset nephrotic syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 18, 2022 | This variant is not present in population databases (gnomAD no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 567126). This variant has not been reported in the literature in individuals affected with LAMB2-related conditions. This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1020 of the LAMB2 protein (p.Ala1020Asp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at