Variant 7-44624382-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_002541.4(OGDH):c.39A>C(p.Pro13Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00679 in 1,602,400 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 5 hom., cov: 30)

Exomes 𝑓: 0.0070 ( 58 hom. )

Consequence

OGDH
NM_002541.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.87

Variant links:

Genes affected

OGDH (HGNC:8124): (oxoglutarate dehydrogenase) This gene encodes one subunit of the 2-oxoglutarate dehydrogenase complex. This complex catalyzes the overall conversion of 2-oxoglutarate (alpha-ketoglutarate) to succinyl-CoA and CO(2) during the Krebs cycle. The protein is located in the mitochondrial matrix and uses thiamine pyrophosphate as a cofactor. A congenital deficiency in 2-oxoglutarate dehydrogenase activity is believed to lead to hypotonia, metabolic acidosis, and hyperlactatemia. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Sep 2009]

OGDH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 7-44624382-A-C is Benign according to our data. Variant chr7-44624382-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 559267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-44624382-A-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.87 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OGDH	NM_002541.4 linkuse as main transcript	c.39A>C	p.Pro13Pro	synonymous_variant	2/23	ENST00000222673.6	NP_002532.2	Q02218-1B4E3E9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OGDH	ENST00000222673.6 linkuse as main transcript	c.39A>C	p.Pro13Pro	synonymous_variant	2/23	1	NM_002541.4	ENSP00000222673.5		Q02218-1

Frequencies

GnomAD3 genomes

AF:

0.00501

AC:

715

AN:

142842

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000946

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00317

Gnomad ASJ

AF:

0.00786

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000663

Gnomad FIN

AF:

0.00648

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00812

Gnomad OTH

AF:

0.00305

GnomAD3 exomes

AF:

0.00513

AC:

1290

AN:

251478

Hom.:

AF XY:

0.00486

AC XY:

660

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.00714

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00183

Gnomad FIN exome

AF:

0.00693

Gnomad NFE exome

AF:

0.00803

Gnomad OTH exome

AF:

0.00407

GnomAD4 exome

AF:

0.00697

AC:

10170

AN:

1459494

Hom.:

Cov.:

AF XY:

0.00678

AC XY:

4921

AN XY:

726078

show subpopulations

Gnomad4 AFR exome

AF:

0.000987

Gnomad4 AMR exome

AF:

0.00206

Gnomad4 ASJ exome

AF:

0.00660

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00175

Gnomad4 FIN exome

AF:

0.00653

Gnomad4 NFE exome

AF:

0.00813

Gnomad4 OTH exome

AF:

0.00564

GnomAD4 genome

AF:

0.00500

AC:

715

AN:

142906

Hom.:

Cov.:

AF XY:

0.00451

AC XY:

309

AN XY:

68568

show subpopulations

Gnomad4 AFR

AF:

0.000943

Gnomad4 AMR

AF:

0.00317

Gnomad4 ASJ

AF:

0.00786

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000666

Gnomad4 FIN

AF:

0.00648

Gnomad4 NFE

AF:

0.00812

Gnomad4 OTH

AF:

0.00302

Alfa

AF:

0.00451

Hom.:

Bravo

AF:

0.00429

EpiCase

AF:

0.00725

EpiControl

AF:

0.00741

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2023	OGDH: BP4, BP7, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 26, 2016	- -

Oxoglutaricaciduria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

OGDH-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 01, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.21

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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