16-56466941-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018233.4(OGFOD1):​c.631G>A​(p.Glu211Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,120 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

OGFOD1
NM_018233.4 missense

Scores

7
6
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.38
Variant links:
Genes affected
OGFOD1 (HGNC:25585): (2-oxoglutarate and iron dependent oxygenase domain containing 1) Enables peptidyl-proline 3-dioxygenase activity. Involved in several processes, including peptidyl-proline hydroxylation; regulation of translational termination; and stress granule assembly. Located in cytoplasmic stress granule; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
BBS2 (HGNC:967): (Bardet-Biedl syndrome 2) This gene is a member of the Bardet-Biedl syndrome (BBS) gene family. Bardet-Biedl syndrome is an autosomal recessive disorder characterized by severe pigmentary retinopathy, obesity, polydactyly, renal malformation and cognitive disability. The proteins encoded by BBS gene family members are structurally diverse and the similar phenotypes exhibited by mutations in BBS gene family members is likely due to their shared roles in cilia formation and function. Many BBS proteins localize to the basal bodies, ciliary axonemes, and pericentriolar regions of cells. BBS proteins may also be involved in intracellular trafficking via microtubule-related transport. The protein encoded by this gene forms a multiprotein BBSome complex with seven other BBS proteins.[provided by RefSeq, Oct 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OGFOD1NM_018233.4 linkuse as main transcriptc.631G>A p.Glu211Lys missense_variant 6/13 ENST00000566157.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OGFOD1ENST00000566157.6 linkuse as main transcriptc.631G>A p.Glu211Lys missense_variant 6/131 NM_018233.4 P1Q8N543-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251346
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135842
show subpopulations
Gnomad AFR exome
AF:
0.000123
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460948
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726848
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152172
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.0000724
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

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 submitterclinical testingAmbry GeneticsNov 17, 2023The c.631G>A (p.E211K) alteration is located in exon 6 (coding exon 6) of the OGFOD1 gene. This alteration results from a G to A substitution at nucleotide position 631, causing the glutamic acid (E) at amino acid position 211 to be replaced by a lysine (K). 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
0.58
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.18
T;T;T
Eigen
Pathogenic
0.80
Eigen_PC
Pathogenic
0.84
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Pathogenic
0.98
D;D;D
M_CAP
Benign
0.021
T
MetaRNN
Uncertain
0.70
D;D;D
MetaSVM
Benign
-0.57
T
MutationAssessor
Uncertain
2.0
M;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.75
T
PROVEAN
Uncertain
-3.9
D;D;D
Sift
Uncertain
0.0050
D;D;D
Sift4G
Benign
0.075
T;D;D
Polyphen
0.94
P;.;.
Vest4
0.90
MutPred
0.50
Gain of methylation at E211 (P = 0.0041);.;Gain of methylation at E211 (P = 0.0041);
MVP
0.78
MPC
0.59
ClinPred
0.81
D
GERP RS
6.2
Varity_R
0.89
gMVP
0.80

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.

Other links and lift over

dbSNP: rs1399117827; hg19: chr16-56500853; API