18-57435934-G-A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004852.3(ONECUT2):​c.218G>A​(p.Gly73Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,193,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G73V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

ONECUT2
NM_004852.3 missense

Scores

1
1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.61

Publications

0 publications found
Variant links:
Genes affected
ONECUT2 (HGNC:8139): (one cut homeobox 2) This gene encodes a member of the onecut family of transcription factors, which are characterized by a cut domain and an atypical homeodomain. The protein binds to specific DNA sequences and stimulates expression of target genes, including genes involved in melanocyte and hepatocyte differentiation. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.15458006).
BS2
High AC in GnomAdExome4 at 63 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ONECUT2NM_004852.3 linkc.218G>A p.Gly73Asp missense_variant Exon 1 of 2 ENST00000491143.3 NP_004843.2 O95948

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ONECUT2ENST00000491143.3 linkc.218G>A p.Gly73Asp missense_variant Exon 1 of 2 1 NM_004852.3 ENSP00000419185.2 O95948

Frequencies

GnomAD3 genomes
AF:
0.0000135
AC:
2
AN:
147626
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000245
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000151
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000602
AC:
63
AN:
1045782
Hom.:
0
Cov.:
34
AF XY:
0.0000709
AC XY:
35
AN XY:
493438
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
21376
American (AMR)
AF:
0.00
AC:
0
AN:
7028
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
12362
East Asian (EAS)
AF:
0.00
AC:
0
AN:
22620
South Asian (SAS)
AF:
0.00
AC:
0
AN:
19520
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
20348
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2698
European-Non Finnish (NFE)
AF:
0.0000690
AC:
62
AN:
898952
Other (OTH)
AF:
0.0000245
AC:
1
AN:
40878
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.482
Heterozygous variant carriers
0
5
10
15
20
25
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<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
AF:
0.0000135
AC:
2
AN:
147626
Hom.:
0
Cov.:
31
AF XY:
0.0000139
AC XY:
1
AN XY:
71856
show subpopulations
African (AFR)
AF:
0.0000245
AC:
1
AN:
40800
American (AMR)
AF:
0.00
AC:
0
AN:
14870
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3404
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5020
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4794
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
9202
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
306
European-Non Finnish (NFE)
AF:
0.0000151
AC:
1
AN:
66294
Other (OTH)
AF:
0.00
AC:
0
AN:
2026
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
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

Genome 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
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.10
T
Eigen
Benign
-0.28
Eigen_PC
Benign
-0.24
FATHMM_MKL
Benign
0.64
D
LIST_S2
Benign
0.40
T
M_CAP
Benign
0.059
D
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
N
PhyloP100
1.6
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-0.82
N
REVEL
Benign
0.061
Sift
Benign
0.030
D
Sift4G
Benign
0.63
T
Polyphen
0.95
P
Vest4
0.21
MutPred
0.14
Loss of MoRF binding (P = 0.1087);
MVP
0.25
MPC
0.90
ClinPred
0.15
T
GERP RS
2.2
Varity_R
0.094
gMVP
0.20
Mutation Taster
=93/7
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs940506922; hg19: chr18-55103166; API