chr11-74343353-C-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_173582.6(PGM2L1):c.1282G>T(p.Glu428Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,708 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_173582.6 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PGM2L1 | NM_173582.6 | c.1282G>T | p.Glu428Ter | stop_gained | 10/14 | ENST00000298198.5 | |
LOC112268078 | XR_002957258.2 | n.314+13865C>A | intron_variant, non_coding_transcript_variant | ||||
PGM2L1 | XM_011544953.4 | c.1345G>T | p.Glu449Ter | stop_gained | 11/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PGM2L1 | ENST00000298198.5 | c.1282G>T | p.Glu428Ter | stop_gained | 10/14 | 1 | NM_173582.6 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000406 AC: 1AN: 246166Hom.: 0 AF XY: 0.00000751 AC XY: 1AN XY: 133192
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1456708Hom.: 0 Cov.: 32 AF XY: 0.00000414 AC XY: 3AN XY: 724666
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 11, 2023 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 10, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1008756). This premature translational stop signal has been observed in individual(s) with PGM2L1-related conditions (PMID: 33979636). This variant is present in population databases (rs767118518, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Glu428*) in the PGM2L1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PGM2L1 are known to be pathogenic (PMID: 33979636). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at