rs117884199
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000426.4(LAMA2):āc.6206A>Gā(p.Tyr2069Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00023 in 1,613,974 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00021 ( 1 hom., cov: 32)
Exomes š: 0.00023 ( 4 hom. )
Consequence
LAMA2
NM_000426.4 missense
NM_000426.4 missense
Scores
7
6
Clinical Significance
Conservation
PhyloP100: 6.77
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.012315601).
BP6
?
Variant 6-129440936-A-G is Benign according to our data. Variant chr6-129440936-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 355285.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00021 (32/152340) while in subpopulation EAS AF= 0.0054 (28/5184). AF 95% confidence interval is 0.00384. There are 1 homozygotes in gnomad4. There are 15 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 4 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.6206A>G | p.Tyr2069Cys | missense_variant | 43/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.6206A>G | p.Tyr2069Cys | missense_variant | 43/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.6206A>G | p.Tyr2069Cys | missense_variant | 43/65 | 5 | NM_000426.4 | ||
ENST00000665046.1 | n.1292T>C | non_coding_transcript_exon_variant | 10/10 | ||||||
LAMA2 | ENST00000618192.5 | c.6470A>G | p.Tyr2157Cys | missense_variant | 44/66 | 5 | P1 | ||
LAMA2 | ENST00000617695.5 | c.6206A>G | p.Tyr2069Cys | missense_variant | 43/64 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000210 AC: 32AN: 152222Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000411 AC: 103AN: 250852Hom.: 1 AF XY: 0.000435 AC XY: 59AN XY: 135560
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GnomAD4 exome AF: 0.000232 AC: 339AN: 1461634Hom.: 4 Cov.: 31 AF XY: 0.000253 AC XY: 184AN XY: 727128
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GnomAD4 genome ? AF: 0.000210 AC: 32AN: 152340Hom.: 1 Cov.: 32 AF XY: 0.000201 AC XY: 15AN XY: 74488
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Congenital muscular dystrophy due to partial LAMA2 deficiency Uncertain:1
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
LAMA2-related muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
LAMA2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 16, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Polyphen
1.0
.;.;D
Vest4
MVP
MPC
0.38
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