Variant 18-57435846-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004852.3(ONECUT2):c.130G>A(p.Gly44Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,002,774 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00078 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0010 ( 3 hom. )

Consequence

ONECUT2
NM_004852.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0480

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028811693).

BP6

Variant 18-57435846-G-A is Benign according to our data. Variant chr18-57435846-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2274640.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 113 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ONECUT2	NM_004852.3 linkuse as main transcript	c.130G>A	p.Gly44Ser	missense_variant	1/2	ENST00000491143.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ONECUT2	ENST00000491143.3 linkuse as main transcript	c.130G>A	p.Gly44Ser	missense_variant	1/2	1	NM_004852.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000777

AC:

113

AN:

145480

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000136

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000633

Gnomad FIN

AF:

0.00325

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00107

Gnomad OTH

AF:

0.00100

GnomAD3 exomes

AF:

0.0186

AC:

AN:

4454

Hom.:

AF XY:

0.0225

AC XY:

AN XY:

2042

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.600

Gnomad FIN exome

AF:

0.00908

Gnomad NFE exome

AF:

0.284

Gnomad OTH exome

AF:

0.100

GnomAD4 exome

AF:

0.00105

AC:

896

AN:

857214

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

427

AN XY:

400406

show subpopulations

Gnomad4 AFR exome

AF:

0.0000626

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00176

Gnomad4 FIN exome

AF:

0.00943

Gnomad4 NFE exome

AF:

0.000997

Gnomad4 OTH exome

AF:

0.000641

GnomAD4 genome

AF:

0.000776

AC:

113

AN:

145560

Hom.:

Cov.:

AF XY:

0.000848

AC XY:

AN XY:

70778

show subpopulations

Gnomad4 AFR

AF:

0.000221

Gnomad4 AMR

AF:

0.000136

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000634

Gnomad4 FIN

AF:

0.00325

Gnomad4 NFE

AF:

0.00107

Gnomad4 OTH

AF:

0.000993

Alfa

AF:

0.000736

Hom.:

Bravo

AF:

0.000495

ExAC

AF:

0.0372

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.96

N;N

PrimateAI

Pathogenic

0.81

REVEL

Benign

0.064

Sift4G

Benign

0.16

Polyphen

0.038

Vest4

0.080

MutPred

0.24

Gain of glycosylation at G44 (P = 9e-04);

MPC

1.6

ClinPred

0.067

GERP RS

1.9

Varity_R

0.10

gMVP

0.40

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over