chr7-44624350-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002541.4(OGDH):c.7C>T(p.His3Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,130,772 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H3R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 18)

Exomes 𝑓: 0.0024 ( 5 hom. )

Consequence

OGDH
NM_002541.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.30

Publications

4 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02072218).

BS2

High Homozygotes in GnomAdExome4 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.7C>T	p.His3Tyr	missense	Exon 2 of 23	NP_002532.2	Q02218-1
OGDH	NM_001439007.1		c.7C>T	p.His3Tyr	missense	Exon 2 of 24	NP_001425936.1
OGDH	NM_001363523.2		c.7C>T	p.His3Tyr	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.7C>T	p.His3Tyr	missense	Exon 2 of 23	ENSP00000222673.5	Q02218-1
OGDH	ENST00000443864.6	TSL:1	c.7C>T	p.His3Tyr	missense	Exon 2 of 9	ENSP00000388084.2	Q02218-3
OGDH	ENST00000962345.1		c.7C>T	p.His3Tyr	missense	Exon 2 of 25	ENSP00000632404.1

Frequencies

GnomAD3 genomes

AF:

0.00205

AC:

156

AN:

75944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000549

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00162

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000411

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00337

Gnomad OTH

AF:

0.00216

GnomAD2 exomes

AF:

0.000888

AC:

182

AN:

204926

AF XY:

0.000872

show subpopulations

Gnomad AFR exome

AF:

0.000250

Gnomad AMR exome

AF:

0.000462

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000474

Gnomad NFE exome

AF:

0.00163

Gnomad OTH exome

AF:

0.00156

GnomAD4 exome

AF:

0.00244

AC:

2573

AN:

1054798

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

1278

AN XY:

512392

show subpopulations

African (AFR)

AF:

0.000205

AC:

AN:

24414

American (AMR)

AF:

0.000721

AC:

AN:

29130

Ashkenazi Jewish (ASJ)

AF:

0.000194

AC:

AN:

15436

East Asian (EAS)

AF:

0.000195

AC:

AN:

20524

South Asian (SAS)

AF:

0.000277

AC:

AN:

50542

European-Finnish (FIN)

AF:

0.000161

AC:

AN:

31140

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2856

European-Non Finnish (NFE)

AF:

0.00289

AC:

2434

AN:

842208

Other (OTH)

AF:

0.00226

AC:

AN:

38548

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

116

233

349

466

582

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<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:

0.00205

AC:

156

AN:

75974

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

AN XY:

34368

show subpopulations

African (AFR)

AF:

0.000548

AC:

AN:

20068

American (AMR)

AF:

0.00162

AC:

AN:

4940

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2208

East Asian (EAS)

AF:

0.00

AC:

AN:

2566

South Asian (SAS)

AF:

0.000413

AC:

AN:

2420

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00337

AC:

134

AN:

39712

Other (OTH)

AF:

0.00214

AC:

AN:

936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00168

Hom.:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.000593

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Oxoglutaricaciduria (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

Eigen

Benign

0.085

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0072

MetaRNN

Benign

0.021

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.7

PhyloP100

2.3

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-2.0

REVEL

Benign

0.089

Sift

Uncertain

0.0070

Sift4G

Benign

0.13

Polyphen

0.19

Vest4

0.45

MVP

0.26

MPC

0.40

ClinPred

0.051

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.48

Mutation Taster

=99/1

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