rs2279096

Positions:

• chr18-57490726-G-A
• chr18-57490726-G-C
• chr18-57490726-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004852.3(ONECUT2):​c.*14003G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 151,916 control chromosomes in the GnomAD database, including 23,916 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.52 (23913 hom., cov: 31)
  • Exomes 𝑓: 0.59 (3 hom.)
• Consequence: ONECUT2 NM_004852.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.666

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ONECUT2	NM_004852.3	c.*14003G>A		3_prime_UTR_variant	2/2	ENST00000491143.3	NP_004843.2
ONECUT2	XM_047437947.1	c.*14214G>A		3_prime_UTR_variant	3/3		XP_047293903.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ONECUT2	ENST00000491143.3	c.*14003G>A		3_prime_UTR_variant	2/2	1	NM_004852.3	ENSP00000419185.2

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79343 AN: 151776 Hom.: 23924 Cov.: 31

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.535

GnomAD4 exome AF: 0.591 AC: 13 AN: 22 Hom.: 3 Cov.: 0 AF XY: 0.500 AC XY: 7 AN XY: 14

Gnomad4 FIN exome AF: 0.650

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.522 AC: 79324 AN: 151894 Hom.: 23913 Cov.: 31 AF XY: 0.517 AC XY: 38398 AN XY: 74242

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.519

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.688

Gnomad4 OTH AF: 0.537

Alfa AF: 0.650 Hom.: 43848

Bravo AF: 0.496

Asia WGS AF: 0.553 AC: 1924 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.67

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

Other links and lift over

dbSNP: rs2279096; hg19: chr18-55157958;