rs940506922

Variant names:

• chr18-57435934-G-A
• rs940506922
• NM_004852.3:c.218G>A

Your query was ambiguous. Multiple possible variants found:

• chr18-57435934-G-A
• chr18-57435934-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• Publications: 0 publications found

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]

ACMG classification

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
ONECUT2	NM_004852.3	c.218G>A	p.Gly73Asp	missense_variant	Exon 1 of 2	ENST00000491143.3	NP_004843.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ONECUT2	ENST00000491143.3	c.218G>A	p.Gly73Asp	missense_variant	Exon 1 of 2	1	NM_004852.3	ENSP00000419185.2

Frequencies

GnomAD3 genomes AF: 0.0000135 AC: 2 AN: 147626 Hom.: 0 Cov.: 31

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

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

GnomAD4 genome AF: 0.0000135 AC: 2 AN: 147626 Hom.: 0 Cov.: 31 AF XY: 0.0000139 AC XY: 1 AN XY: 71856

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

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

Other links and lift over

dbSNP: rs940506922; hg19: chr18-55103166;