rs564306903
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7
The NM_024884.3(L2HGDH):c.627A>G(p.Ala209=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,614,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000057 ( 0 hom. )
Consequence
L2HGDH
NM_024884.3 synonymous
NM_024884.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.262
Genes affected
L2HGDH (HGNC:20499): (L-2-hydroxyglutarate dehydrogenase) This gene encodes L-2-hydroxyglutarate dehydrogenase, a FAD-dependent enzyme that oxidizes L-2-hydroxyglutarate to alpha-ketoglutarate in a variety of mammalian tissues. Mutations in this gene cause L-2-hydroxyglutaric aciduria, a rare autosomal recessive neurometabolic disorder resulting in moderate to severe cognitive disability. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
Variant 14-50283947-T-C is Benign according to our data. Variant chr14-50283947-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 158800.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}. Variant chr14-50283947-T-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.262 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
L2HGDH | NM_024884.3 | c.627A>G | p.Ala209= | synonymous_variant | 5/10 | ENST00000267436.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
L2HGDH | ENST00000267436.9 | c.627A>G | p.Ala209= | synonymous_variant | 5/10 | 1 | NM_024884.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152222Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251380Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135872
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GnomAD4 exome AF: 0.0000575 AC: 84AN: 1461832Hom.: 0 Cov.: 32 AF XY: 0.0000564 AC XY: 41AN XY: 727216
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152340Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2AN XY: 74492
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
L-2-hydroxyglutaric aciduria Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 10, 2014 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at