Variant 7-44645449-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_002541.4(OGDH):c.345A>G(p.Glu115Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0233 in 1,614,148 control chromosomes in the GnomAD database, including 672 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.037 ( 148 hom., cov: 32)

Exomes 𝑓: 0.022 ( 524 hom. )

Consequence

OGDH
NM_002541.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -3.41

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 7-44645449-A-G is Benign according to our data. Variant chr7-44645449-A-G is described in ClinVar as [Benign]. Clinvar id is 559268.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OGDH	NM_002541.4 linkuse as main transcript	c.345A>G	p.Glu115Glu	synonymous_variant	3/23	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.345A>G	p.Glu115Glu	synonymous_variant	3/23	1	NM_002541.4	ENSP00000222673.5		Q02218-1

Frequencies

GnomAD3 genomes

AF:

0.0367

AC:

5591

AN:

152178

Hom.:

147

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0711

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0343

Gnomad ASJ

AF:

0.0490

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.00703

Gnomad FIN

AF:

0.00970

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0246

Gnomad OTH

AF:

0.0455

GnomAD3 exomes

AF:

0.0234

AC:

5879

AN:

251308

Hom.:

117

AF XY:

0.0220

AC XY:

2995

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.0729

Gnomad AMR exome

AF:

0.0230

Gnomad ASJ exome

AF:

0.0474

Gnomad EAS exome

AF:

0.00169

Gnomad SAS exome

AF:

0.00647

Gnomad FIN exome

AF:

0.00878

Gnomad NFE exome

AF:

0.0247

Gnomad OTH exome

AF:

0.0315

GnomAD4 exome

AF:

0.0219

AC:

32018

AN:

1461852

Hom.:

524

Cov.:

AF XY:

0.0217

AC XY:

15796

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0752

Gnomad4 AMR exome

AF:

0.0239

Gnomad4 ASJ exome

AF:

0.0458

Gnomad4 EAS exome

AF:

0.00202

Gnomad4 SAS exome

AF:

0.00705

Gnomad4 FIN exome

AF:

0.0107

Gnomad4 NFE exome

AF:

0.0217

Gnomad4 OTH exome

AF:

0.0265

GnomAD4 genome

AF:

0.0367

AC:

5594

AN:

152296

Hom.:

148

Cov.:

AF XY:

0.0351

AC XY:

2614

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0710

Gnomad4 AMR

AF:

0.0342

Gnomad4 ASJ

AF:

0.0490

Gnomad4 EAS

AF:

0.00309

Gnomad4 SAS

AF:

0.00663

Gnomad4 FIN

AF:

0.00970

Gnomad4 NFE

AF:

0.0246

Gnomad4 OTH

AF:

0.0450

Alfa

AF:

0.0342

Hom.:

Bravo

AF:

0.0397

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0282

EpiControl

AF:

0.0271

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Oxoglutaricaciduria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

not provided

Benign:1

Benign, no assertion criteria provided

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Feb 22, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.76

DANN

Benign

0.54

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