rs752674803
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002292.4(LAMB2):āc.4877G>Cā(p.Arg1626Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1626Q) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMB2 | NM_002292.4 | c.4877G>C | p.Arg1626Pro | missense_variant | 29/32 | ENST00000305544.9 | |
LAMB2 | XM_005265127.5 | c.4877G>C | p.Arg1626Pro | missense_variant | 30/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMB2 | ENST00000305544.9 | c.4877G>C | p.Arg1626Pro | missense_variant | 29/32 | 1 | NM_002292.4 | P1 | |
LAMB2 | ENST00000418109.5 | c.4877G>C | p.Arg1626Pro | missense_variant | 30/33 | 1 | P1 | ||
LAMB2 | ENST00000498377.1 | n.532G>C | non_coding_transcript_exon_variant | 2/5 | 2 | ||||
LAMB2 | ENST00000467506.5 | upstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461608Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727138
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 09, 2022 | 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: 472490). This variant has not been reported in the literature in individuals affected with LAMB2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 1626 of the LAMB2 protein (p.Arg1626Pro). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at