Variant chr12-122978951-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001304833.2(OGFOD2):c.730A>G(p.Asn244Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OGFOD2
NM_001304833.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32

Variant links:

Genes affected

OGFOD2 (HGNC:25823): (2-oxoglutarate and iron dependent oxygenase domain containing 2) Predicted to enable several functions, including L-ascorbic acid binding activity; dioxygenase activity; and iron ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

OGFOD2 links:

ABCB9 (HGNC:50): (ATP binding cassette subfamily B member 9) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance as well as antigen presentation. This family member functions in the translocation of peptides from the cytosol into the lysosomal lumen. Alternative splicing of this gene results in distinct isoforms which are likely to have different substrate specificities. [provided by RefSeq, Jul 2011]

ABCB9 links:

OGFOD2 (HGNC:):

OGFOD2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.977

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OGFOD2	NM_001304833.2 linkuse as main transcript	c.730A>G	p.Asn244Asp	missense_variant	6/7	ENST00000228922.12	NP_001291762.1	Q6N063-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OGFOD2	ENST00000228922.12 linkuse as main transcript	c.730A>G	p.Asn244Asp	missense_variant	6/7	1	NM_001304833.2	ENSP00000228922.7		Q6N063-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1460988

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726806

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 26, 2024

The c.550A>G (p.N184D) alteration is located in exon 7 (coding exon 5) of the OGFOD2 gene. This alteration results from a A to G substitution at nucleotide position 550, causing the asparagine (N) at amino acid position 184 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

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

Eigen

Pathogenic

0.72

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

D;.;.;.;.;.;.;D;D;D

M_CAP

Pathogenic

0.39

MetaRNN

Pathogenic

0.98

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

MetaSVM

Pathogenic

0.98

MutationAssessor

Pathogenic

3.0

.;.;.;.;.;.;.;.;M;.

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-4.7

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

REVEL

Pathogenic

0.77

Sift

Uncertain

0.010

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

Sift4G

Uncertain

0.017

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

Polyphen

1.0

D;.;.;.;.;.;.;.;D;.

Vest4

0.97

MutPred

0.89

.;.;.;.;.;.;.;.;Gain of sheet (P = 0.0827);.;

MVP

0.58

MPC

0.28

ClinPred

0.99

GERP RS

5.3

Varity_R

0.57

gMVP

0.93

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over