NM_006494.4:c.891_892delAG
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_006494.4(ERF):c.891_892delAG(p.Gly299ArgfsTer9) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,262 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
ERF
NM_006494.4 frameshift
NM_006494.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.18
Publications
7 publications found
Genes affected
ERF (HGNC:3444): (ETS2 repressor factor) ETS2 is a transcription factor and protooncogene involved in development, apoptosis, and the regulation of telomerase. The protein encoded by this gene binds to the ETS2 promoter and is a strong repressor of ETS2 transcription. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]
ERF Gene-Disease associations (from GenCC):
- Chitayat syndromeInheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
- craniosynostosis 4Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, Ambry Genetics, G2P
- Crouzon syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- isolated scaphocephalyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 14 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 13 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-42249219-CCT-C is Pathogenic according to our data. Variant chr19-42249219-CCT-C is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 55924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_006494.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ERF | MANE Select | c.891_892delAG | p.Gly299ArgfsTer9 | frameshift | Exon 4 of 4 | NP_006485.2 | P50548-1 | ||
| ERF | c.666_667delAG | p.Gly224ArgfsTer9 | frameshift | Exon 4 of 4 | NP_001287964.1 | P50548-2 | |||
| ERF | c.666_667delAG | p.Gly224ArgfsTer9 | frameshift | Exon 4 of 4 | NP_001295331.1 | P50548-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ERF | TSL:1 MANE Select | c.891_892delAG | p.Gly299ArgfsTer9 | frameshift | Exon 4 of 4 | ENSP00000222329.3 | P50548-1 | ||
| ENSG00000268643 | TSL:3 | c.22+5757_22+5758delAG | intron | N/A | ENSP00000470087.1 | M0QYV0 | |||
| ERF | TSL:2 | c.666_667delAG | p.Gly224ArgfsTer9 | frameshift | Exon 4 of 4 | ENSP00000388173.2 | P50548-2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461262Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 726936 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1461262
Hom.:
AF XY:
AC XY:
0
AN XY:
726936
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33474
American (AMR)
AF:
AC:
0
AN:
44680
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26116
East Asian (EAS)
AF:
AC:
0
AN:
39672
South Asian (SAS)
AF:
AC:
0
AN:
86238
European-Finnish (FIN)
AF:
AC:
0
AN:
53222
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111754
Other (OTH)
AF:
AC:
0
AN:
60338
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic/Likely pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
4
-
-
Craniosynostosis 4 (4)
1
-
-
Chitayat syndrome (1)
1
-
-
Craniosynostosis 4;C4310679:Chitayat syndrome (1)
1
-
-
Inborn genetic diseases (1)
1
-
-
Noonan-like syndrome (1)
1
-
-
not provided (1)
1
-
-
See cases (1)
1
-
-
TWIST1-related craniosynostosis (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.