chr6-129143875-G-A
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000426.4(LAMA2):c.640-26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,502,734 control chromosomes in the GnomAD database, including 33,958 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.25 ( 5257 hom., cov: 32)
Exomes 𝑓: 0.20 ( 28701 hom. )
Consequence
LAMA2
NM_000426.4 intron
NM_000426.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.303
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 6-129143875-G-A is Benign according to our data. Variant chr6-129143875-G-A is described in ClinVar as [Benign]. Clinvar id is 256079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129143875-G-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.640-26G>A | intron_variant | ENST00000421865.3 | |||
LAMA2 | NM_001079823.2 | c.640-26G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.640-26G>A | intron_variant | 5 | NM_000426.4 |
Frequencies
GnomAD3 genomes AF: 0.247 AC: 37442AN: 151730Hom.: 5257 Cov.: 32
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GnomAD3 exomes AF: 0.193 AC: 45623AN: 236086Hom.: 4790 AF XY: 0.196 AC XY: 25072AN XY: 127618
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GnomAD4 exome AF: 0.202 AC: 272252AN: 1350886Hom.: 28701 Cov.: 20 AF XY: 0.203 AC XY: 137054AN XY: 676704
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GnomAD4 genome AF: 0.247 AC: 37480AN: 151848Hom.: 5257 Cov.: 32 AF XY: 0.244 AC XY: 18108AN XY: 74222
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2018 | 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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
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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