6-129328306-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_000426.4(LAMA2):c.4205G>A(p.Arg1402His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,614,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1402C) has been classified as Uncertain significance.
Frequency
Consequence
NM_000426.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.4205G>A | p.Arg1402His | missense_variant | 29/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.4205G>A | p.Arg1402His | missense_variant | 29/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.4205G>A | p.Arg1402His | missense_variant | 29/65 | 5 | NM_000426.4 | ||
LAMA2 | ENST00000618192.5 | c.4469G>A | p.Arg1490His | missense_variant | 30/66 | 5 | P1 | ||
LAMA2 | ENST00000617695.5 | c.4205G>A | p.Arg1402His | missense_variant | 29/64 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000237 AC: 36AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251334Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135842
GnomAD4 exome AF: 0.000127 AC: 185AN: 1461844Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 88AN XY: 727224
GnomAD4 genome AF: 0.000236 AC: 36AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74464
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 22, 2022 | The c.4205G>A (p.R1402H) alteration is located in exon 29 (coding exon 29) of the LAMA2 gene. This alteration results from a G to A substitution at nucleotide position 4205, causing the arginine (R) at amino acid position 1402 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 02, 2022 | - - |
Congenital muscular dystrophy due to partial LAMA2 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
Merosin deficient congenital muscular dystrophy;C4748327:Muscular dystrophy, limb-girdle, autosomal recessive 23 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 26, 2021 | - - |
LAMA2-related muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at