NM_002541.4:c.164C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002541.4(OGDH):c.164C>T(p.Ser55Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00824 in 1,613,744 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0065 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0084 ( 74 hom. )

Consequence

OGDH
NM_002541.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.79

Publications

15 publications found

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 Gene-Disease associations (from GenCC):

oxoglutaricaciduria
Inheritance: AR, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

OGDH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008775711).

BP6

Variant 7-44624507-C-T is Benign according to our data. Variant chr7-44624507-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 780042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002541.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OGDH	NM_002541.4	MANE Select	c.164C>T	p.Ser55Leu	missense	Exon 2 of 23	NP_002532.2	Q02218-1
OGDH	NM_001439007.1		c.164C>T	p.Ser55Leu	missense	Exon 2 of 24	NP_001425936.1
OGDH	NM_001363523.2		c.164C>T	p.Ser55Leu	missense	Exon 2 of 24	NP_001350452.1	E9PDF2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OGDH	ENST00000222673.6	TSL:1 MANE Select	c.164C>T	p.Ser55Leu	missense	Exon 2 of 23	ENSP00000222673.5	Q02218-1
OGDH	ENST00000443864.6	TSL:1	c.164C>T	p.Ser55Leu	missense	Exon 2 of 9	ENSP00000388084.2	Q02218-3
OGDH	ENST00000962345.1		c.164C>T	p.Ser55Leu	missense	Exon 2 of 25	ENSP00000632404.1

Frequencies

GnomAD3 genomes

AF:

0.00650

AC:

986

AN:

151770

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.00565

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00541

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0102

Gnomad OTH

AF:

0.00576

GnomAD2 exomes

AF:

0.00683

AC:

1716

AN:

251406

AF XY:

0.00701

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00520

Gnomad ASJ exome

AF:

0.00595

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00587

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.00978

GnomAD4 exome

AF:

0.00842

AC:

12311

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00830

AC XY:

6034

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.00116

AC:

AN:

33480

American (AMR)

AF:

0.00525

AC:

235

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00635

AC:

166

AN:

26136

East Asian (EAS)

AF:

0.000529

AC:

AN:

39700

South Asian (SAS)

AF:

0.00174

AC:

150

AN:

86252

European-Finnish (FIN)

AF:

0.00689

AC:

368

AN:

53420

Middle Eastern (MID)

AF:

0.0108

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00971

AC:

10803

AN:

1112000

Other (OTH)

AF:

0.00773

AC:

467

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

689

1378

2068

2757

3446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

398

796

1194

1592

1990

<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:

0.00649

AC:

986

AN:

151888

Hom.:

Cov.:

AF XY:

0.00632

AC XY:

469

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.00133

AC:

AN:

41420

American (AMR)

AF:

0.00564

AC:

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.00893

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00104

AC:

AN:

4788

European-Finnish (FIN)

AF:

0.00541

AC:

AN:

10542

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0102

AC:

692

AN:

67938

Other (OTH)

AF:

0.00570

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

148

197

246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00868

Hom.:

Bravo

AF:

0.00665

TwinsUK

AF:

0.0113

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00895

AC:

ExAC

AF:

0.00726

AC:

882

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0115

EpiControl

AF:

0.0112

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

OGDH-related disorder (1)

Oxoglutaricaciduria (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0079

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0088

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.0

PhyloP100

5.8

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.0

REVEL

Benign

0.24

Sift

Uncertain

0.0020

Sift4G

Benign

0.073

Polyphen

0.20

Vest4

0.68

MVP

0.59

MPC

0.47

ClinPred

0.025

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.76

gMVP

0.72

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over