rs754156525
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_002292.4(LAMB2):c.5346C>T(p.Ser1782Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000959 in 1,460,308 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: not found (cov: 33)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
LAMB2
NM_002292.4 synonymous
NM_002292.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.793
Publications
1 publications found
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]
LAMB2 Gene-Disease associations (from GenCC):
- Pierson syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, PanelApp Australia, Orphanet
- LAMB2-related infantile-onset nephrotic syndromeInheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
Variant 3-49121277-G-A is Benign according to our data. Variant chr3-49121277-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1088162.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.793 with no splicing effect.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.0000199 AC: 5AN: 251346 AF XY: 0.0000294 show subpopulations
GnomAD2 exomes
AF:
AC:
5
AN:
251346
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000959 AC: 14AN: 1460308Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 726466 show subpopulations
GnomAD4 exome
AF:
AC:
14
AN:
1460308
Hom.:
Cov.:
32
AF XY:
AC XY:
10
AN XY:
726466
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33434
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
10
AN:
86184
European-Finnish (FIN)
AF:
AC:
0
AN:
53378
Middle Eastern (MID)
AF:
AC:
0
AN:
4498
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1112004
Other (OTH)
AF:
AC:
2
AN:
60252
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Asia WGS
AF:
AC:
1
AN:
3478
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
Jan 27, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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