rs2229848
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000426.4(LAMA2):c.7760C>T(p.Ala2587Val) variant causes a missense change. The variant allele was found at a frequency of 0.695 in 1,612,146 control chromosomes in the GnomAD database, including 393,345 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.63 ( 31327 hom., cov: 32)
Exomes 𝑓: 0.70 ( 362018 hom. )
Consequence
LAMA2
NM_000426.4 missense
NM_000426.4 missense
Scores
4
7
6
Clinical Significance
Conservation
PhyloP100: 4.63
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 (MetaRNN=1.0597179E-5).
BP6
Variant 6-129486484-C-T is Benign according to our data. Variant chr6-129486484-C-T is described in ClinVar as [Benign]. Clinvar id is 167247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129486484-C-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.7760C>T | p.Ala2587Val | missense_variant | 56/65 | ENST00000421865.3 | NP_000417.3 | |
LAMA2 | NM_001079823.2 | c.7748C>T | p.Ala2583Val | missense_variant | 55/64 | NP_001073291.2 | ||
LOC124901401 | XR_007059767.1 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.7760C>T | p.Ala2587Val | missense_variant | 56/65 | 5 | NM_000426.4 | ENSP00000400365 | ||
ENST00000665046.1 | n.975+16121G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.632 AC: 95962AN: 151854Hom.: 31302 Cov.: 32
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GnomAD3 exomes AF: 0.672 AC: 168513AN: 250778Hom.: 57254 AF XY: 0.677 AC XY: 91681AN XY: 135520
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GnomAD4 exome AF: 0.702 AC: 1024939AN: 1460174Hom.: 362018 Cov.: 43 AF XY: 0.701 AC XY: 509109AN XY: 726458
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GnomAD4 genome AF: 0.632 AC: 96029AN: 151972Hom.: 31327 Cov.: 32 AF XY: 0.630 AC XY: 46794AN XY: 74256
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 03, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 20, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Merosin deficient congenital muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
LAMA2-related muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
.;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
.;.;M
MutationTaster
Benign
P
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;.;D
REVEL
Uncertain
Sift
Benign
.;.;T
Polyphen
1.0
.;.;D
Vest4
MPC
0.45
ClinPred
T
GERP RS
Varity_R
gMVP
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