3-49123216-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002292.4(LAMB2):c.4140C>A(p.Asn1380Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000426 in 1,613,902 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMB2 | ENST00000305544.9 | c.4140C>A | p.Asn1380Lys | missense_variant | Exon 26 of 32 | 1 | NM_002292.4 | ENSP00000307156.4 | ||
LAMB2 | ENST00000418109.5 | c.4140C>A | p.Asn1380Lys | missense_variant | Exon 27 of 33 | 1 | ENSP00000388325.1 | |||
LAMB2 | ENST00000469665.1 | n.370C>A | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 | |||||
LAMB2 | ENST00000477225.1 | n.*109C>A | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.000256 AC: 39AN: 152258Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000251 AC: 63AN: 251456Hom.: 0 AF XY: 0.000221 AC XY: 30AN XY: 135908
GnomAD4 exome AF: 0.000443 AC: 648AN: 1461644Hom.: 1 Cov.: 34 AF XY: 0.000436 AC XY: 317AN XY: 727136
GnomAD4 genome AF: 0.000256 AC: 39AN: 152258Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74382
ClinVar
Submissions by phenotype
Pierson syndrome;C3280113:LAMB2-related infantile-onset nephrotic syndrome Uncertain:2
This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 1380 of the LAMB2 protein (p.Asn1380Lys). This variant is present in population databases (rs267607207, gnomAD 0.06%). This missense change has been observed in individual(s) with congenital nephrotic syndrome (PMID: 16912710). ClinVar contains an entry for this variant (Variation ID: 242783). 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 tolerated. 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. -
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LAMB2-related infantile-onset nephrotic syndrome Uncertain:1
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. -
Pierson syndrome Uncertain:1
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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at