dbSNP rs1486605675: ONECUT2:p.Gly54Asp (chr18-57435877-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004852.3(ONECUT2):c.161G>A(p.Gly54Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000019 in 1,050,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. G54V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000011 ( 0 hom. )

Consequence

ONECUT2
NM_004852.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.459

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]

ONECUT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11618611).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ONECUT2	NM_004852.3 link	c.161G>A	p.Gly54Asp	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
ONECUT2	ENST00000491143.3 link	c.161G>A	p.Gly54Asp	missense_variant	Exon 1 of 2	1	NM_004852.3	ENSP00000419185.2		O95948

Frequencies

GnomAD3 genomes

AF:

0.00000687

AC:

AN:

145588

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000110

AC:

AN:

905062

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

425464

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17334

American (AMR)

AF:

0.00

AC:

AN:

2960

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6852

East Asian (EAS)

AF:

0.00

AC:

AN:

7502

South Asian (SAS)

AF:

0.00

AC:

AN:

18028

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10522

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1932

European-Non Finnish (NFE)

AF:

0.00000124

AC:

AN:

808658

Other (OTH)

AF:

0.00

AC:

AN:

31274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000686

AC:

AN:

145686

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

70884

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40716

American (AMR)

AF:

0.00

AC:

AN:

14702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3378

East Asian (EAS)

AF:

0.00

AC:

AN:

4976

South Asian (SAS)

AF:

0.000210

AC:

AN:

4770

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8352

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65566

Other (OTH)

AF:

0.00

AC:

AN:

2030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.11

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.40

M_CAP

Benign

0.064

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.46

PrimateAI

Uncertain

0.79

PROVEAN

Benign

0.23

REVEL

Benign

0.064

Sift

Benign

0.30

Sift4G

Benign

0.67

Polyphen

0.28

Vest4

0.21

MutPred

0.19

Loss of glycosylation at P55 (P = 0.0777);

MVP

0.51

MPC

0.95

ClinPred

0.064

GERP RS

1.0

Varity_R

0.088

gMVP

0.41

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs1486605675

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over