chr6-129267114-G-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000426.4(LAMA2):c.2217G>T(p.Trp739Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00037 in 1,608,450 control chromosomes in the GnomAD database, including 3 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
Consequence
NM_000426.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.2217G>T | p.Trp739Cys | missense_variant | Exon 16 of 65 | 5 | NM_000426.4 | ENSP00000400365.2 | ||
LAMA2 | ENST00000618192.5 | c.2217G>T | p.Trp739Cys | missense_variant | Exon 16 of 66 | 5 | ENSP00000480802.2 | |||
LAMA2 | ENST00000617695.5 | c.2217G>T | p.Trp739Cys | missense_variant | Exon 16 of 64 | 5 | ENSP00000481744.2 |
Frequencies
GnomAD3 genomes AF: 0.000540 AC: 82AN: 151974Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00105 AC: 264AN: 251002Hom.: 0 AF XY: 0.000966 AC XY: 131AN XY: 135626
GnomAD4 exome AF: 0.000352 AC: 513AN: 1456358Hom.: 3 Cov.: 30 AF XY: 0.000375 AC XY: 272AN XY: 724864
GnomAD4 genome AF: 0.000539 AC: 82AN: 152092Hom.: 0 Cov.: 32 AF XY: 0.000646 AC XY: 48AN XY: 74354
ClinVar
Submissions by phenotype
Merosin deficient congenital muscular dystrophy Uncertain:1
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not provided Uncertain:1
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Congenital muscular dystrophy due to partial LAMA2 deficiency Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
not specified Benign:1
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LAMA2-related muscular dystrophy Benign:1
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Muscular dystrophy, limb-girdle, autosomal recessive 23 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at