Variant rs2297995 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024884.3(L2HGDH):c.159C>T(p.Ile53Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 1,607,172 control chromosomes in the GnomAD database, including 261,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 25453 hom., cov: 33)

Exomes 𝑓: 0.57 ( 235695 hom. )

Consequence

L2HGDH
NM_024884.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.255

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 14-50302999-G-A is Benign according to our data. Variant chr14-50302999-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 158798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-50302999-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.255 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.639 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.159C>T	p.Ile53Ile	synonymous_variant	2/10	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.159C>T	p.Ile53Ile	synonymous_variant	2/10	1	NM_024884.3	ENSP00000267436.4		Q9H9P8-1

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87816

AN:

151968

Hom.:

25406

Cov.:

show subpopulations

Gnomad AFR

AF:

0.615

Gnomad AMI

AF:

0.509

Gnomad AMR

AF:

0.499

Gnomad ASJ

AF:

0.526

Gnomad EAS

AF:

0.657

Gnomad SAS

AF:

0.567

Gnomad FIN

AF:

0.584

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.571

Gnomad OTH

AF:

0.567

GnomAD3 exomes

AF:

0.565

AC:

141964

AN:

251298

Hom.:

40420

AF XY:

0.566

AC XY:

76891

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.621

Gnomad AMR exome

AF:

0.479

Gnomad ASJ exome

AF:

0.514

Gnomad EAS exome

AF:

0.658

Gnomad SAS exome

AF:

0.571

Gnomad FIN exome

AF:

0.582

Gnomad NFE exome

AF:

0.568

Gnomad OTH exome

AF:

0.554

GnomAD4 exome

AF:

0.568

AC:

826137

AN:

1455086

Hom.:

235695

Cov.:

AF XY:

0.567

AC XY:

410874

AN XY:

724312

show subpopulations

Gnomad4 AFR exome

AF:

0.619

Gnomad4 AMR exome

AF:

0.485

Gnomad4 ASJ exome

AF:

0.513

Gnomad4 EAS exome

AF:

0.642

Gnomad4 SAS exome

AF:

0.573

Gnomad4 FIN exome

AF:

0.583

Gnomad4 NFE exome

AF:

0.567

Gnomad4 OTH exome

AF:

0.574

GnomAD4 genome

AF:

0.578

AC:

87927

AN:

152086

Hom.:

25453

Cov.:

AF XY:

0.576

AC XY:

42794

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.615

Gnomad4 AMR

AF:

0.500

Gnomad4 ASJ

AF:

0.526

Gnomad4 EAS

AF:

0.657

Gnomad4 SAS

AF:

0.567

Gnomad4 FIN

AF:

0.584

Gnomad4 NFE

AF:

0.571

Gnomad4 OTH

AF:

0.567

Alfa

AF:

0.565

Hom.:

45343

Bravo

AF:

0.570

Asia WGS

AF:

0.581

AC:

2021

AN:

3478

EpiCase

AF:

0.560

EpiControl

AF:

0.563

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 19, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

1.2

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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