16-56466941-G-A
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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
NM_018233.4 missense
Scores
7
6
5
Clinical Significance
Conservation
PhyloP100: 9.38
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]
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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 |
---|---|---|---|---|---|---|---|
OGFOD1 | NM_018233.4 | c.631G>A | p.Glu211Lys | missense_variant | 6/13 | ENST00000566157.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OGFOD1 | ENST00000566157.6 | c.631G>A | p.Glu211Lys | missense_variant | 6/13 | 1 | NM_018233.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251346Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135842
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460948Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726848
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74336
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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 | Nov 17, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
Sift
Uncertain
D;D;D
Sift4G
Benign
T;D;D
Polyphen
P;.;.
Vest4
MutPred
Gain of methylation at E211 (P = 0.0041);.;Gain of methylation at E211 (P = 0.0041);
MVP
MPC
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at