3-49121420-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_002292.4(LAMB2):c.5260+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,613,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000064 ( 0 hom. )
Consequence
LAMB2
NM_002292.4 intron
NM_002292.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.460
Genes affected
LAMB2 (HGNC:6487): (laminin subunit beta 2) Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins, composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively), form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the beta chain isoform laminin, beta 2. The beta 2 chain contains the 7 structural domains typical of beta chains of laminin, including the short alpha region. However, unlike beta 1 chain, beta 2 has a more restricted tissue distribution. It is enriched in the basement membrane of muscles at the neuromuscular junctions, kidney glomerulus and vascular smooth muscle. Transgenic mice in which the beta 2 chain gene was inactivated by homologous recombination, showed defects in the maturation of neuromuscular junctions and impairment of glomerular filtration. Alternative splicing involving a non consensus 5' splice site (gc) in the 5' UTR of this gene has been reported. It was suggested that inefficient splicing of this first intron, which does not change the protein sequence, results in a greater abundance of the unspliced form of the transcript than the spliced form. The full-length nature of the spliced transcript is not known. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
Variant 3-49121420-C-T is Benign according to our data. Variant chr3-49121420-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1626510.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| LAMB2 | NM_002292.4 | c.5260+13G>A | intron_variant | ENST00000305544.9 | |||
| LAMB2 | XM_005265127.5 | c.5260+13G>A | intron_variant |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| LAMB2 | ENST00000305544.9 | c.5260+13G>A | intron_variant | 1 | NM_002292.4 | P1 |
Frequencies
GnomAD3 genomes 0.0000526 AC: 8AN: 152186Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251444Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135908
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GnomAD4 exome AF: 0.0000643 AC: 94AN: 1461782Hom.: 0 Cov.: 33 AF XY: 0.0000578 AC XY: 42AN XY: 727204
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GnomAD4 genome 0.0000526 AC: 8AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74350
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Pierson syndrome;C3280113:LAMB2-related infantile-onset nephrotic syndrome Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 08, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at