rs756535650
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_ModerateBP6BP7BS1
The ENST00000305544.9(LAMB2):c.2152C>T(p.Leu718=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,611,902 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L718L) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000305544.9 splice_region, synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LAMB2 | NM_002292.4 | c.2152C>T | p.Leu718= | splice_region_variant, synonymous_variant | 17/32 | ENST00000305544.9 | NP_002283.3 | |
LAMB2 | XM_005265127.5 | c.2152C>T | p.Leu718= | splice_region_variant, synonymous_variant | 18/33 | XP_005265184.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMB2 | ENST00000305544.9 | c.2152C>T | p.Leu718= | splice_region_variant, synonymous_variant | 17/32 | 1 | NM_002292.4 | ENSP00000307156 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000643 AC: 16AN: 248942Hom.: 0 AF XY: 0.0000891 AC XY: 12AN XY: 134646
GnomAD4 exome AF: 0.000114 AC: 166AN: 1459686Hom.: 1 Cov.: 32 AF XY: 0.000128 AC XY: 93AN XY: 726116
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74362
ClinVar
Submissions by phenotype
Pierson syndrome;C3280113:LAMB2-related infantile-onset nephrotic syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 03, 2023 | This sequence change affects codon 718 of the LAMB2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the LAMB2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs756535650, gnomAD 0.02%). This variant has been observed in individual(s) with LAMB2-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 258602). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at