rs369408727
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_002292.4(LAMB2):c.1750C>T(p.Arg584Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,613,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R584S) has been classified as Uncertain significance.
Frequency
Consequence
NM_002292.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMB2 | NM_002292.4 | c.1750C>T | p.Arg584Cys | missense_variant | 14/32 | ENST00000305544.9 | |
LAMB2 | XM_005265127.5 | c.1750C>T | p.Arg584Cys | missense_variant | 15/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMB2 | ENST00000305544.9 | c.1750C>T | p.Arg584Cys | missense_variant | 14/32 | 1 | NM_002292.4 | P1 | |
LAMB2 | ENST00000418109.5 | c.1750C>T | p.Arg584Cys | missense_variant | 15/33 | 1 | P1 | ||
LAMB2 | ENST00000483321.1 | n.180C>T | non_coding_transcript_exon_variant | 3/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152170Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250768Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135582
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461044Hom.: 0 Cov.: 36 AF XY: 0.0000248 AC XY: 18AN XY: 726710
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152170Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74334
ClinVar
Submissions by phenotype
Pierson syndrome;C3280113:LAMB2-related infantile-onset nephrotic syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 25, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 25, 2023 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1407293). This variant has not been reported in the literature in individuals affected with LAMB2-related conditions. This variant is present in population databases (rs369408727, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 584 of the LAMB2 protein (p.Arg584Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at