rs587777274
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PP2PP3_StrongPP5_Moderate
The NM_005654.6(NR2F1):c.344G>C(p.Arg115Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 30)
Consequence
NR2F1
NM_005654.6 missense
NM_005654.6 missense
Scores
12
6
1
Clinical Significance
Conservation
PhyloP100: 6.63
Genes affected
NR2F1 (HGNC:7975): (nuclear receptor subfamily 2 group F member 1) The protein encoded by this gene is a nuclear hormone receptor and transcriptional regulator. The encoded protein acts as a homodimer and binds to 5'-AGGTCA-3' repeats. Defects in this gene are a cause of Bosch-Boonstra optic atrophy syndrome (BBOAS). [provided by RefSeq, Apr 2014]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PM1
In a DNA_binding_region Nuclear receptor (size 75) in uniprot entity COT1_HUMAN there are 10 pathogenic changes around while only 0 benign (100%) in NM_005654.6
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the NR2F1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 51 curated pathogenic missense variants (we use a threshold of 10). The gene has 7 curated benign missense variants. Gene score misZ: 4.1652 (above the threshold of 3.09). Trascript score misZ: 4.6855 (above the threshold of 3.09). GenCC associations: The gene is linked to Bosch-Boonstra-Schaaf optic atrophy syndrome.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.976
PP5
Variant 5-93585367-G-C is Pathogenic according to our data. Variant chr5-93585367-G-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 126493.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-93585367-G-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
30
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
GnomAD4 genome
Cov.:
30
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Bosch-Boonstra-Schaaf optic atrophy syndrome Pathogenic:3
Feb 06, 2014
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: research
- -
Sep 09, 2015
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine
Significance: Pathogenic
Review Status: criteria provided, single submitter
Collection Method: research
This study shows that diverse genetic causes underlie CVI. -
Feb 06, 2014
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;D;.;D
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M;.;.
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
.;D;.;.
REVEL
Pathogenic
Sift
Pathogenic
.;D;.;.
Sift4G
Uncertain
.;D;.;D
Polyphen
D;D;.;.
Vest4
0.76, 0.76
MutPred
Loss of MoRF binding (P = 0.0124);Loss of MoRF binding (P = 0.0124);.;.;
MVP
0.98
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at