chr6-129445671-C-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS1
The NM_000426.4(LAMA2):c.6279C>T(p.Ala2093=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00067 in 1,613,644 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 0.0016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00057 ( 0 hom. )
Consequence
LAMA2
NM_000426.4 synonymous
NM_000426.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.01
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 -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
Variant 6-129445671-C-T is Benign according to our data. Variant chr6-129445671-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 477499.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1, Benign=1}. Variant chr6-129445671-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=1.01 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00164 (250/152222) while in subpopulation AFR AF= 0.00441 (183/41520). AF 95% confidence interval is 0.00389. There are 0 homozygotes in gnomad4. There are 112 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.6279C>T | p.Ala2093= | synonymous_variant | 45/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.6279C>T | p.Ala2093= | synonymous_variant | 45/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.6279C>T | p.Ala2093= | synonymous_variant | 45/65 | 5 | NM_000426.4 | ||
ENST00000665046.1 | n.976-4419G>A | intron_variant, non_coding_transcript_variant | |||||||
LAMA2 | ENST00000618192.5 | c.6543C>T | p.Ala2181= | synonymous_variant | 46/66 | 5 | P1 | ||
LAMA2 | ENST00000617695.5 | c.6279C>T | p.Ala2093= | synonymous_variant | 45/64 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00164 AC: 249AN: 152104Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000834 AC: 209AN: 250598Hom.: 0 AF XY: 0.000783 AC XY: 106AN XY: 135446
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GnomAD4 exome AF: 0.000569 AC: 831AN: 1461422Hom.: 0 Cov.: 31 AF XY: 0.000541 AC XY: 393AN XY: 727024
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GnomAD4 genome AF: 0.00164 AC: 250AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.00150 AC XY: 112AN XY: 74430
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 25, 2021 | This variant is associated with the following publications: (PMID: 21896784) - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | LAMA2: BP4, BP7 - |
Congenital muscular dystrophy due to partial LAMA2 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
LAMA2-related muscular dystrophy Benign:1
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 20, 2020 | 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
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