rs147291222
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_000426.4(LAMA2):āc.3628A>Gā(p.Ile1210Val) variant causes a missense change. The variant allele was found at a frequency of 0.000108 in 1,614,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00016 ( 0 hom., cov: 32)
Exomes š: 0.00010 ( 0 hom. )
Consequence
LAMA2
NM_000426.4 missense
NM_000426.4 missense
Scores
1
12
Clinical Significance
Conservation
PhyloP100: 3.84
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 Likely_benign. Variant got -4 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.050245762).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.3628A>G | p.Ile1210Val | missense_variant | 25/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.3628A>G | p.Ile1210Val | missense_variant | 25/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.3628A>G | p.Ile1210Val | missense_variant | 25/65 | 5 | NM_000426.4 | ||
LAMA2 | ENST00000618192.5 | c.3892A>G | p.Ile1298Val | missense_variant | 26/66 | 5 | P1 | ||
LAMA2 | ENST00000617695.5 | c.3628A>G | p.Ile1210Val | missense_variant | 25/64 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152214Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000171 AC: 43AN: 251474Hom.: 0 AF XY: 0.000132 AC XY: 18AN XY: 135906
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GnomAD4 exome AF: 0.000103 AC: 150AN: 1461872Hom.: 0 Cov.: 32 AF XY: 0.000110 AC XY: 80AN XY: 727232
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GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152332Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74504
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:4Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 20, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 05, 2022 | Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). Computational tools predict that this variant is not damaging. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Apr 05, 2021 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 02, 2023 | The c.3628A>G (p.I1210V) alteration is located in exon 25 (coding exon 25) of the LAMA2 gene. This alteration results from a A to G substitution at nucleotide position 3628, causing the isoleucine (I) at amino acid position 1210 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
LAMA2-related muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Benign
T
Polyphen
0.076
.;.;B
Vest4
MVP
MPC
0.076
ClinPred
T
GERP RS
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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