rs200658738
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002292.4(LAMB2):c.2236C>T(p.Arg746Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000527 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R746H) has been classified 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMB2 | NM_002292.4 | c.2236C>T | p.Arg746Cys | missense_variant | 17/32 | ENST00000305544.9 | |
LAMB2 | XM_005265127.5 | c.2236C>T | p.Arg746Cys | missense_variant | 18/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMB2 | ENST00000305544.9 | c.2236C>T | p.Arg746Cys | missense_variant | 17/32 | 1 | NM_002292.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000717 AC: 18AN: 251124Hom.: 0 AF XY: 0.0000737 AC XY: 10AN XY: 135762
GnomAD4 exome AF: 0.0000527 AC: 77AN: 1461802Hom.: 0 Cov.: 32 AF XY: 0.0000619 AC XY: 45AN XY: 727192
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152260Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74458
ClinVar
Submissions by phenotype
Pierson syndrome;C3280113:LAMB2-related infantile-onset nephrotic syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 23, 2017 | This sequence change replaces arginine with cysteine at codon 746 of the LAMB2 protein (p.Arg746Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs200658738, ExAC 0.04%) but has not been reported in the literature in individuals with a LAMB2-related disease. 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 disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 04, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at