14-77027231-G-A
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_024496.4(IRF2BPL):c.562C>T(p.Arg188*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. 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: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
IRF2BPL
NM_024496.4 stop_gained
NM_024496.4 stop_gained
Scores
2
3
1
Clinical Significance
Conservation
PhyloP100: 0.947
Publications
4 publications found
Genes affected
IRF2BPL (HGNC:14282): (interferon regulatory factor 2 binding protein like) This gene encodes a transcription factor that may play a role in regulating female reproductive function. [provided by RefSeq, Jun 2012]
LINC02289 (HGNC:53205): (long intergenic non-protein coding RNA 2289)
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 55 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 14-77027231-G-A is Pathogenic according to our data. Variant chr14-77027231-G-A is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 559608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_024496.4. You can select a different transcript below to see updated ACMG assignments.
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00000433 AC: 1AN: 230838 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
230838
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1449506Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0AN XY: 720854
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1449506
Hom.:
Cov.:
37
AF XY:
AC XY:
0
AN XY:
720854
African (AFR)
AF:
AC:
0
AN:
32418
American (AMR)
AF:
AC:
0
AN:
43126
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25508
East Asian (EAS)
AF:
AC:
0
AN:
38662
South Asian (SAS)
AF:
AC:
0
AN:
85310
European-Finnish (FIN)
AF:
AC:
0
AN:
52418
Middle Eastern (MID)
AF:
AC:
0
AN:
5516
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1106824
Other (OTH)
AF:
AC:
0
AN:
59724
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic/Likely pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
4
-
-
Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures (4)
1
-
-
Inborn genetic diseases (1)
1
-
-
IRF2BPL-related disorder (1)
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
PhyloP100
Vest4
GERP RS
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
Publications
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