rs142264176
Positions:
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6
The NM_000426.4(LAMA2):c.6229G>A(p.Ala2077Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000288 in 1,613,632 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A2077A) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00029 ( 0 hom. )
Consequence
LAMA2
NM_000426.4 missense
NM_000426.4 missense
Scores
4
9
Clinical Significance
Conservation
PhyloP100: 4.79
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 -1 ACMG points.
BP6
?
Variant 6-129440959-G-A is Benign according to our data. Variant chr6-129440959-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 440937.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1, not_provided=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.6229G>A | p.Ala2077Thr | missense_variant | 43/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.6229G>A | p.Ala2077Thr | missense_variant | 43/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.6229G>A | p.Ala2077Thr | missense_variant | 43/65 | 5 | NM_000426.4 | ||
ENST00000665046.1 | n.1269C>T | non_coding_transcript_exon_variant | 10/10 | ||||||
LAMA2 | ENST00000618192.5 | c.6493G>A | p.Ala2165Thr | missense_variant | 44/66 | 5 | P1 | ||
LAMA2 | ENST00000617695.5 | c.6229G>A | p.Ala2077Thr | missense_variant | 43/64 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000250 AC: 38AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000877 AC: 22AN: 250838Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135550
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GnomAD4 exome AF: 0.000291 AC: 426AN: 1461478Hom.: 0 Cov.: 31 AF XY: 0.000271 AC XY: 197AN XY: 727038
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GnomAD4 genome ? AF: 0.000250 AC: 38AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74322
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1Other:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 08, 2018 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jan 04, 2023 | - - |
LAMA2-related muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Merosin deficient congenital muscular dystrophy Other:1
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Benign
T
Polyphen
0.94
.;.;P
Vest4
MVP
MPC
0.11
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