Variant rs12433038 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0670

Variant links:

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 links:

L2HGDH (HGNC:):

L2HGDH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr14-50283859-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
L2HGDH	NM_024884.3 linkuse as main transcript	c.703+12T>C		intron_variant		ENST00000267436.9	NP_079160.1	Q9H9P8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
L2HGDH	ENST00000267436.9 linkuse as main transcript	c.703+12T>C		intron_variant		1	NM_024884.3	ENSP00000267436.4		Q9H9P8-1

Frequencies

GnomAD3 genomes

AF:

0.509

AC:

77264

AN:

151846

Hom.:

20171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.397

Gnomad AMI

AF:

0.509

Gnomad AMR

AF:

0.447

Gnomad ASJ

AF:

0.507

Gnomad EAS

AF:

0.651

Gnomad SAS

AF:

0.531

Gnomad FIN

AF:

0.584

Gnomad MID

AF:

0.510

Gnomad NFE

AF:

0.567

Gnomad OTH

AF:

0.511

GnomAD3 exomes

AF:

0.538

AC:

135080

AN:

251222

Hom.:

36973

AF XY:

0.543

AC XY:

73799

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.394

Gnomad AMR exome

AF:

0.441

Gnomad ASJ exome

AF:

0.496

Gnomad EAS exome

AF:

0.653

Gnomad SAS exome

AF:

0.540

Gnomad FIN exome

AF:

0.582

Gnomad NFE exome

AF:

0.564

Gnomad OTH exome

AF:

0.531

GnomAD4 exome

AF:

0.555

AC:

809721

AN:

1457778

Hom.:

226572

Cov.:

AF XY:

0.555

AC XY:

402762

AN XY:

725462

show subpopulations

Gnomad4 AFR exome

AF:

0.390

Gnomad4 AMR exome

AF:

0.444

Gnomad4 ASJ exome

AF:

0.495

Gnomad4 EAS exome

AF:

0.636

Gnomad4 SAS exome

AF:

0.542

Gnomad4 FIN exome

AF:

0.583

Gnomad4 NFE exome

AF:

0.564

Gnomad4 OTH exome

AF:

0.546

GnomAD4 genome

AF:

0.509

AC:

77351

AN:

151966

Hom.:

20202

Cov.:

AF XY:

0.508

AC XY:

37763

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.397

Gnomad4 AMR

AF:

0.448

Gnomad4 ASJ

AF:

0.507

Gnomad4 EAS

AF:

0.652

Gnomad4 SAS

AF:

0.532

Gnomad4 FIN

AF:

0.584

Gnomad4 NFE

AF:

0.567

Gnomad4 OTH

AF:

0.511

Alfa

AF:

0.537

Hom.:

6273

Bravo

AF:

0.493

Asia WGS

AF:

0.524

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 31, 2013

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.3

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over