rs73775410
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_000426.4(LAMA2):c.6274+4C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00459 in 1,591,668 control chromosomes in the GnomAD database, including 303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.026 ( 173 hom., cov: 32)
Exomes 𝑓: 0.0024 ( 130 hom. )
Consequence
LAMA2
NM_000426.4 splice_donor_region, intron
NM_000426.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0008636
2
Clinical Significance
Conservation
PhyloP100: 0.300
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 -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
?
Variant 6-129443072-C-T is Benign according to our data. Variant chr6-129443072-C-T is described in ClinVar as [Benign]. Clinvar id is 355286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129443072-C-T is described in Lovd as [Benign]. Variant chr6-129443072-C-T is described in Lovd as [Likely_benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.087 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.6274+4C>T | splice_donor_region_variant, intron_variant | ENST00000421865.3 | |||
LAMA2 | NM_001079823.2 | c.6274+4C>T | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.6274+4C>T | splice_donor_region_variant, intron_variant | 5 | NM_000426.4 | ||||
ENST00000665046.1 | n.976-1820G>A | intron_variant, non_coding_transcript_variant | |||||||
LAMA2 | ENST00000617695.5 | c.6274+4C>T | splice_donor_region_variant, intron_variant | 5 | |||||
LAMA2 | ENST00000618192.5 | c.6538+4C>T | splice_donor_region_variant, intron_variant | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0257 AC: 3904AN: 151916Hom.: 172 Cov.: 32
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GnomAD3 exomes AF: 0.00652 AC: 1586AN: 243404Hom.: 62 AF XY: 0.00460 AC XY: 606AN XY: 131714
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GnomAD4 exome AF: 0.00235 AC: 3386AN: 1439636Hom.: 130 Cov.: 26 AF XY: 0.00206 AC XY: 1476AN XY: 716894
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GnomAD4 genome ? AF: 0.0258 AC: 3919AN: 152032Hom.: 173 Cov.: 32 AF XY: 0.0252 AC XY: 1876AN XY: 74300
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 21, 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. - |
LAMA2-related muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 20, 2017 | - - |
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. - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at