rs201806251
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1
The NM_024884.3(L2HGDH):c.137C>T(p.Thr46Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000314 in 1,563,862 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_024884.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
L2HGDH | NM_024884.3 | c.137C>T | p.Thr46Ile | missense_variant | 1/10 | ENST00000267436.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
L2HGDH | ENST00000267436.9 | c.137C>T | p.Thr46Ile | missense_variant | 1/10 | 1 | NM_024884.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00141 AC: 214AN: 152188Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000387 AC: 64AN: 165552Hom.: 0 AF XY: 0.000310 AC XY: 28AN XY: 90194
GnomAD4 exome AF: 0.000196 AC: 277AN: 1411556Hom.: 0 Cov.: 31 AF XY: 0.000185 AC XY: 129AN XY: 698248
GnomAD4 genome AF: 0.00141 AC: 214AN: 152306Hom.: 1 Cov.: 32 AF XY: 0.00133 AC XY: 99AN XY: 74482
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 10, 2018 | - - |
L-2-hydroxyglutaric aciduria Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
L2HGDH-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 02, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at