rs371376404
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6BP7
The NM_000426.4(LAMA2):c.3279C>T(p.Cys1093=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,906 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
LAMA2
NM_000426.4 synonymous
NM_000426.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.87
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 Likely_benign. Variant got -4 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
?
Variant 6-129312965-C-T is Benign according to our data. Variant chr6-129312965-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211352.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=1.87 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.3279C>T | p.Cys1093= | synonymous_variant | 23/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.3279C>T | p.Cys1093= | synonymous_variant | 23/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.3279C>T | p.Cys1093= | synonymous_variant | 23/65 | 5 | NM_000426.4 | ||
LAMA2 | ENST00000618192.5 | c.3543C>T | p.Cys1181= | synonymous_variant | 24/66 | 5 | P1 | ||
LAMA2 | ENST00000617695.5 | c.3279C>T | p.Cys1093= | synonymous_variant | 23/64 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152196Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251468Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135908
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461710Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727164
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152196Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74346
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 17, 2015 | - - |
Merosin deficient congenital muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Nov 17, 2017 | - - |
LAMA2-related muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
LAMA2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 02, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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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