chr14-50283859-A-G
Variant names:
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_024884.3(L2HGDH):c.703+12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 1,609,744 control chromosomes in the GnomAD database, including 246,774 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.51 ( 20202 hom., cov: 31)
Exomes 𝑓: 0.56 ( 226572 hom. )
Consequence
L2HGDH
NM_024884.3 intron
NM_024884.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0670
Publications
16 publications found
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]
L2HGDH Gene-Disease associations (from GenCC):
- L-2-hydroxyglutaric aciduriaInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
- mitochondrial diseaseInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 14-50283859-A-G is Benign according to our data. Variant chr14-50283859-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 158801.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.509 AC: 77264AN: 151846Hom.: 20171 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
77264
AN:
151846
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.538 AC: 135080AN: 251222 AF XY: 0.543 show subpopulations
GnomAD2 exomes
AF:
AC:
135080
AN:
251222
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.555 AC: 809721AN: 1457778Hom.: 226572 Cov.: 32 AF XY: 0.555 AC XY: 402762AN XY: 725462 show subpopulations
GnomAD4 exome
AF:
AC:
809721
AN:
1457778
Hom.:
Cov.:
32
AF XY:
AC XY:
402762
AN XY:
725462
show subpopulations
African (AFR)
AF:
AC:
13037
AN:
33404
American (AMR)
AF:
AC:
19869
AN:
44702
Ashkenazi Jewish (ASJ)
AF:
AC:
12906
AN:
26094
East Asian (EAS)
AF:
AC:
25244
AN:
39664
South Asian (SAS)
AF:
AC:
46669
AN:
86132
European-Finnish (FIN)
AF:
AC:
31105
AN:
53356
Middle Eastern (MID)
AF:
AC:
2620
AN:
5752
European-Non Finnish (NFE)
AF:
AC:
625377
AN:
1108440
Other (OTH)
AF:
AC:
32894
AN:
60234
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.471
Heterozygous variant carriers
0
15949
31897
47846
63794
79743
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Exome Hom
Variant carriers
0
17348
34696
52044
69392
86740
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome AF: 0.509 AC: 77351AN: 151966Hom.: 20202 Cov.: 31 AF XY: 0.508 AC XY: 37763AN XY: 74276 show subpopulations
GnomAD4 genome
AF:
AC:
77351
AN:
151966
Hom.:
Cov.:
31
AF XY:
AC XY:
37763
AN XY:
74276
show subpopulations
African (AFR)
AF:
AC:
16461
AN:
41416
American (AMR)
AF:
AC:
6839
AN:
15268
Ashkenazi Jewish (ASJ)
AF:
AC:
1759
AN:
3470
East Asian (EAS)
AF:
AC:
3365
AN:
5164
South Asian (SAS)
AF:
AC:
2566
AN:
4824
European-Finnish (FIN)
AF:
AC:
6158
AN:
10552
Middle Eastern (MID)
AF:
AC:
148
AN:
292
European-Non Finnish (NFE)
AF:
AC:
38514
AN:
67962
Other (OTH)
AF:
AC:
1080
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1887
3774
5662
7549
9436
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
692
1384
2076
2768
3460
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1820
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
L-2-hydroxyglutaric aciduria Benign:2
Aug 19, 2021
Genome-Nilou Lab
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
not specified Benign:1
Oct 31, 2013
Genetic Services Laboratory, University of Chicago
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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