rs372715292
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate
The NM_000426.4(LAMA2):c.3736-2A>G variant causes a splice acceptor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_000426.4 splice_acceptor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.3736-2A>G | splice_acceptor_variant | ENST00000421865.3 | NP_000417.3 | |||
LAMA2 | NM_001079823.2 | c.3736-2A>G | splice_acceptor_variant | NP_001073291.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.3736-2A>G | splice_acceptor_variant | 5 | NM_000426.4 | ENSP00000400365 | ||||
LAMA2 | ENST00000617695.5 | c.3736-2A>G | splice_acceptor_variant | 5 | ENSP00000481744 | |||||
LAMA2 | ENST00000618192.5 | c.4000-2A>G | splice_acceptor_variant | 5 | ENSP00000480802 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251228Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135846
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461716Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727172
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Merosin deficient congenital muscular dystrophy Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jan 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at