rs1555810408
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_006420.3(ARFGEF2):c.1426-8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
ARFGEF2
NM_006420.3 splice_region, intron
NM_006420.3 splice_region, intron
Scores
2
Splicing: ADA: 0.00008713
2
Clinical Significance
Conservation
PhyloP100: 0.855
Publications
0 publications found
Genes affected
ARFGEF2 (HGNC:15853): (ADP ribosylation factor guanine nucleotide exchange factor 2) ADP-ribosylation factors (ARFs) play an important role in intracellular vesicular trafficking. The protein encoded by this gene is involved in the activation of ARFs by accelerating replacement of bound GDP with GTP and is involved in Golgi transport. It contains a Sec7 domain, which may be responsible for its guanine-nucleotide exchange activity and also brefeldin A inhibition. [provided by RefSeq, Jul 2008]
ARFGEF2 Gene-Disease associations (from GenCC):
- periventricular heterotopia with microcephaly, autosomal recessiveInheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen
- periventricular nodular heterotopiaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| ARFGEF2 | NM_006420.3 | c.1426-8T>C | splice_region_variant, intron_variant | Intron 10 of 38 | ENST00000371917.5 | NP_006411.2 | ||
| ARFGEF2 | NM_001410846.1 | c.1423-8T>C | splice_region_variant, intron_variant | Intron 10 of 38 | NP_001397775.1 | |||
| ARFGEF2 | XM_047439832.1 | c.862-8T>C | splice_region_variant, intron_variant | Intron 8 of 36 | XP_047295788.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| ARFGEF2 | ENST00000371917.5 | c.1426-8T>C | splice_region_variant, intron_variant | Intron 10 of 38 | 1 | NM_006420.3 | ENSP00000360985.4 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.92e-7 AC: 1AN: 1444302Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 719934 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1444302
Hom.:
Cov.:
28
AF XY:
AC XY:
0
AN XY:
719934
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33120
American (AMR)
AF:
AC:
0
AN:
44700
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26028
East Asian (EAS)
AF:
AC:
0
AN:
39608
South Asian (SAS)
AF:
AC:
0
AN:
85914
European-Finnish (FIN)
AF:
AC:
0
AN:
53372
Middle Eastern (MID)
AF:
AC:
0
AN:
5702
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1096104
Other (OTH)
AF:
AC:
1
AN:
59754
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
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
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Sep 26, 2016
Genetic Services Laboratory, University of Chicago
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
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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