9-6413540-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_152896.3(UHRF2):āc.50A>Gā(p.Glu17Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,443,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
UHRF2
NM_152896.3 missense
NM_152896.3 missense
Scores
1
2
16
Clinical Significance
Conservation
PhyloP100: 8.32
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16919029).
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
UHRF2 | ENST00000276893.10 | c.50A>G | p.Glu17Gly | missense_variant | 1/16 | 1 | NM_152896.3 | ENSP00000276893.5 | ||
UHRF2 | ENST00000468435.6 | n.50A>G | non_coding_transcript_exon_variant | 1/17 | 1 | ENSP00000434182.1 | ||||
UHRF2 | ENST00000381373.3 | c.50A>G | p.Glu17Gly | missense_variant | 1/3 | 3 | ENSP00000370778.3 | |||
UHRF2 | ENST00000469298.5 | n.221A>G | non_coding_transcript_exon_variant | 2/4 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000856 AC: 2AN: 233654Hom.: 0 AF XY: 0.00000786 AC XY: 1AN XY: 127182
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GnomAD4 exome AF: 0.00000208 AC: 3AN: 1443914Hom.: 0 Cov.: 31 AF XY: 0.00000418 AC XY: 3AN XY: 718236
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ExAC
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1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 15, 2023 | The c.50A>G (p.E17G) alteration is located in exon 1 (coding exon 1) of the UHRF2 gene. This alteration results from a A to G substitution at nucleotide position 50, causing the glutamic acid (E) at amino acid position 17 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;D
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;D
Polyphen
B;.
Vest4
MutPred
Loss of stability (P = 0.0402);Loss of stability (P = 0.0402);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at