14-50237660-ATGT-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PM4_SupportingBP6_ModerateBS1BS2
The ENST00000261699.8(L2HGDH):c.1259_1261del(p.Asn420del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 1,609,136 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0018 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0024 ( 11 hom. )
Consequence
L2HGDH
ENST00000261699.8 inframe_deletion
ENST00000261699.8 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.05
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 Benign. Variant got -9 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in ENST00000261699.8. Strenght limited to Supporting due to length of the change: 1aa.
BP6
?
Variant 14-50237660-ATGT-A is Benign according to our data. Variant chr14-50237660-ATGT-A is described in ClinVar as [Likely_benign]. Clinvar id is 1694718.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00176 (268/152276) while in subpopulation SAS AF= 0.00435 (21/4826). AF 95% confidence interval is 0.00292. There are 0 homozygotes in gnomad4. There are 145 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
L2HGDH | ENST00000261699.8 | c.1259_1261del | p.Asn420del | inframe_deletion | 10/10 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00177 AC: 270AN: 152158Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00220 AC: 518AN: 235274Hom.: 2 AF XY: 0.00256 AC XY: 331AN XY: 129070
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GnomAD4 exome AF: 0.00244 AC: 3555AN: 1456860Hom.: 11 AF XY: 0.00253 AC XY: 1831AN XY: 724292
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2022 | L2HGDH: BS2 - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at