6-129098399-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_000426.4(LAMA2):c.623C>A(p.Pro208His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,613,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P208P) has been classified as Likely benign.
Frequency
Consequence
NM_000426.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.623C>A | p.Pro208His | missense_variant | 4/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.623C>A | p.Pro208His | missense_variant | 4/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.623C>A | p.Pro208His | missense_variant | 4/65 | 5 | NM_000426.4 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152024Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000183 AC: 46AN: 251290Hom.: 0 AF XY: 0.000214 AC XY: 29AN XY: 135826
GnomAD4 exome AF: 0.000133 AC: 194AN: 1461732Hom.: 0 Cov.: 31 AF XY: 0.000149 AC XY: 108AN XY: 727184
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74378
ClinVar
Submissions by phenotype
not provided Uncertain:4
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Apr 22, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Aug 03, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 13, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 10, 2019 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2022 | The c.623C>A (p.P208H) alteration is located in exon 4 (coding exon 4) of the LAMA2 gene. This alteration results from a C to A substitution at nucleotide position 623, causing the proline (P) at amino acid position 208 to be replaced by a histidine (H). 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 | Dec 30, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at