rs200718262
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000426.4(LAMA2):c.8692A>C(p.Arg2898=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000213 in 1,612,990 control chromosomes in the GnomAD database, including 4 homozygotes. 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 0.0011 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 1 hom. )
Consequence
LAMA2
NM_000426.4 synonymous
NM_000426.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.61
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
Variant 6-129505344-A-C is Benign according to our data. Variant chr6-129505344-A-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 92993.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00114 (174/152310) while in subpopulation AMR AF= 0.0112 (172/15298). AF 95% confidence interval is 0.00987. There are 3 homozygotes in gnomad4. There are 119 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 3 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.8692A>C | p.Arg2898= | synonymous_variant | 61/65 | ENST00000421865.3 | |
LOC102723409 | XR_001743860.2 | n.12103-2553T>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.8692A>C | p.Arg2898= | synonymous_variant | 61/65 | 5 | NM_000426.4 | ||
ENST00000665046.1 | n.789-2553T>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00114 AC: 174AN: 152192Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.000366 AC: 92AN: 251236Hom.: 0 AF XY: 0.000324 AC XY: 44AN XY: 135772
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GnomAD4 exome AF: 0.000116 AC: 169AN: 1460680Hom.: 1 Cov.: 30 AF XY: 0.000102 AC XY: 74AN XY: 726782
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 17, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 19, 2017 | - - |
LAMA2-related muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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Name
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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