Variant 7-44624351-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_002541.4(OGDH):c.8A>G(p.His3Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000773 in 1,461,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., cov: 24)

Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

OGDH
NM_002541.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.63

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), OGDH. . Gene score misZ 4.7595 (greater than the threshold 3.09). Trascript score misZ 5.6536 (greater than threshold 3.09). GenCC has associacion of gene with oxoglutaricaciduria.

BP4

Computational evidence support a benign effect (MetaRNN=0.08025682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OGDH	NM_002541.4 linkuse as main transcript	c.8A>G	p.His3Arg	missense_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.8A>G	p.His3Arg	missense_variant	2/23	1	NM_002541.4	ENSP00000222673.5		Q02218-1

Frequencies

GnomAD3 genomes

AF:

0.0000177

AC:

AN:

112744

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000356

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000174

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000203

AC:

AN:

246820

Hom.:

AF XY:

0.0000299

AC XY:

AN XY:

133628

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000450

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000823

AC:

111

AN:

1348734

Hom.:

Cov.:

AF XY:

0.0000768

AC XY:

AN XY:

663702

show subpopulations

Gnomad4 AFR exome

AF:

0.0000651

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.0000366

GnomAD4 genome

AF:

0.0000177

AC:

AN:

112744

Hom.:

Cov.:

AF XY:

0.0000192

AC XY:

AN XY:

52092

show subpopulations

Gnomad4 AFR

AF:

0.0000356

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000174

Gnomad4 OTH

AF:

0.00

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Dec 08, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.33

DEOGEN2

Benign

0.0054

T;.;.;.;T;T;T;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.92

D;D;D;D;D;D;D;D

M_CAP

Benign

0.0029

MetaRNN

Benign

0.080

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.14

.;N;.;N;.;.;.;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.62

N;N;N;N;N;N;.;N

REVEL

Benign

0.23

Sift

Benign

0.18

T;T;T;T;T;T;.;T

Sift4G

Benign

1.0

T;T;T;T;T;T;T;T

Polyphen

0.0

B;.;B;.;.;.;.;B

Vest4

0.29

MVP

0.65

MPC

0.37

ClinPred

0.078

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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