rs3749877
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000426.4(LAMA2):āc.5466A>Gā(p.Glu1822=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 1,580,252 control chromosomes in the GnomAD database, including 181,718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.51 ( 20116 hom., cov: 32)
Exomes š: 0.47 ( 161602 hom. )
Consequence
LAMA2
NM_000426.4 synonymous
NM_000426.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.00
Genes affected
LAMA2 (HGNC:6482): (laminin subunit alpha 2) Laminin, an extracellular protein, is a major component of the basement membrane. It is thought to mediate the attachment, migration, and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. It is composed of three subunits, alpha, beta, and gamma, which are bound to each other by disulfide bonds into a cross-shaped molecule. This gene encodes the alpha 2 chain, which constitutes one of the subunits of laminin 2 (merosin) and laminin 4 (s-merosin). Mutations in this gene have been identified as the cause of congenital merosin-deficient muscular dystrophy. Two transcript variants encoding different proteins have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
Variant 6-129401244-A-G is Benign according to our data. Variant chr6-129401244-A-G is described in ClinVar as [Benign]. Clinvar id is 92966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129401244-A-G is described in Lovd as [Benign]. Variant chr6-129401244-A-G is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.5466A>G | p.Glu1822= | synonymous_variant | 38/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.5466A>G | p.Glu1822= | synonymous_variant | 38/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.5466A>G | p.Glu1822= | synonymous_variant | 38/65 | 5 | NM_000426.4 | ||
LAMA2 | ENST00000618192.5 | c.5730A>G | p.Glu1910= | synonymous_variant | 39/66 | 5 | P1 | ||
LAMA2 | ENST00000617695.5 | c.5466A>G | p.Glu1822= | synonymous_variant | 38/64 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.508 AC: 77162AN: 151922Hom.: 20073 Cov.: 32
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GnomAD3 exomes AF: 0.494 AC: 124058AN: 251072Hom.: 31198 AF XY: 0.493 AC XY: 66913AN XY: 135694
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GnomAD4 exome AF: 0.469 AC: 670335AN: 1428212Hom.: 161602 Cov.: 32 AF XY: 0.471 AC XY: 335371AN XY: 712156
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GnomAD4 genome ? AF: 0.508 AC: 77275AN: 152040Hom.: 20116 Cov.: 32 AF XY: 0.509 AC XY: 37828AN XY: 74318
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ClinVar
Significance: Benign
Submissions summary: Benign:12
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 18, 2012 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 15, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 05, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Merosin deficient congenital muscular dystrophy Benign:3
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 19, 2021 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 13, 2017 | - - |
LAMA2-related muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Congenital muscular dystrophy due to partial LAMA2 deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Muscular dystrophy, limb-girdle, autosomal recessive 23 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 19, 2021 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at