rs2297738
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000426.4(LAMA2):c.6237G>A(p.Thr2079=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,612,810 control chromosomes in the GnomAD database, including 21,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.16 ( 2159 hom., cov: 32)
Exomes 𝑓: 0.16 ( 19787 hom. )
Consequence
LAMA2
NM_000426.4 synonymous
NM_000426.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.70
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 6-129440967-G-A is Benign according to our data. Variant chr6-129440967-G-A is described in ClinVar as [Benign]. Clinvar id is 92975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129440967-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=1.7 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.6237G>A | p.Thr2079= | synonymous_variant | 43/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.6237G>A | p.Thr2079= | synonymous_variant | 43/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.6237G>A | p.Thr2079= | synonymous_variant | 43/65 | 5 | NM_000426.4 | ||
ENST00000665046.1 | n.1261C>T | non_coding_transcript_exon_variant | 10/10 | ||||||
LAMA2 | ENST00000618192.5 | c.6501G>A | p.Thr2167= | synonymous_variant | 44/66 | 5 | P1 | ||
LAMA2 | ENST00000617695.5 | c.6237G>A | p.Thr2079= | synonymous_variant | 43/64 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.163 AC: 24773AN: 152000Hom.: 2159 Cov.: 32
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GnomAD3 exomes AF: 0.173 AC: 43412AN: 250786Hom.: 3973 AF XY: 0.171 AC XY: 23144AN XY: 135544
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GnomAD4 exome AF: 0.163 AC: 237679AN: 1460692Hom.: 19787 Cov.: 33 AF XY: 0.163 AC XY: 118245AN XY: 726738
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GnomAD4 genome ? AF: 0.163 AC: 24777AN: 152118Hom.: 2159 Cov.: 32 AF XY: 0.167 AC XY: 12387AN XY: 74362
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 15, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 05, 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. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 20, 2016 | - - |
LAMA2-related muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
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
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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