chr9-6486308-G-C

Position:

• chr9-6486308-G-C

Variant summary

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

The NM_152896.3(UHRF2):​c.1393-513G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,124 control chromosomes in the GnomAD database, including 2,323 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 0.17 (2323 hom., cov: 32)
• Consequence: UHRF2 NM_152896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UHRF2	NM_152896.3	c.1393-513G>C		intron_variant		ENST00000276893.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UHRF2	ENST00000276893.10	c.1393-513G>C		intron_variant		1	NM_152896.3	P1
UHRF2	ENST00000468435.6	c.1393-513G>C		intron_variant, NMD_transcript_variant		1
UHRF2	ENST00000477183.1	n.140-513G>C		intron_variant, non_coding_transcript_variant		3
UHRF2	ENST00000484159.5	n.835-513G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25703 AN: 152006 Hom.: 2327 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.169 AC: 25706 AN: 152124 Hom.: 2323 Cov.: 32 AF XY: 0.174 AC XY: 12905 AN XY: 74364

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.174

Alfa AF: 0.166 Hom.: 283

Bravo AF: 0.167

Asia WGS AF: 0.208 AC: 724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.4
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs16924631; hg19: chr9-6486308;