rs7020390

Positions:

• chr9-6470921-A-G
• chr9-6470921-A-T

Variant summary

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

The NM_152896.3(UHRF2):​c.864-4470A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 152,038 control chromosomes in the GnomAD database, including 25,382 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 0.56 (25382 hom., cov: 32)
• Consequence: UHRF2 NM_152896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.826

Genes affected

UHRF2 (HGNC:12557): (ubiquitin like with PHD and ring finger domains 2) This gene encodes a nuclear protein which is involved in cell-cycle regulation. The encoded protein is a ubiquitin-ligase capable of ubiquinating PCNP (PEST-containing nuclear protein), and together they may play a role in tumorigenesis. The encoded protein contains an NIRF_N domain, a PHD finger, a set- and ring-associated (SRA) domain, and a RING finger domain and several of these domains have been shown to be essential for the regulation of cell proliferation. This protein may also have a role in intranuclear degradation of polyglutamine aggregates. Alternative splicing results in multiple transcript variants some of which are non-protein coding. [provided by RefSeq, Feb 2012]

UHRF2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UHRF2	NM_152896.3	c.864-4470A>G		intron_variant		ENST00000276893.10	NP_690856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UHRF2	ENST00000276893.10	c.864-4470A>G		intron_variant		1	NM_152896.3	ENSP00000276893.5
UHRF2	ENST00000468435.6	n.864-4470A>G		intron_variant		1		ENSP00000434182.1
UHRF2	ENST00000450508.1	c.195-4470A>G		intron_variant		3		ENSP00000399217.2
UHRF2	ENST00000484159.5	n.306-4470A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84757 AN: 151920 Hom.: 25321 Cov.: 32

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.547

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.558 AC: 84863 AN: 152038 Hom.: 25382 Cov.: 32 AF XY: 0.561 AC XY: 41666 AN XY: 74334

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.545

Alfa AF: 0.522 Hom.: 5769

Bravo AF: 0.574

Asia WGS AF: 0.413 AC: 1437 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.53
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: rs7020390; hg19: chr9-6470921; COSMIC: COSV52792731;