1-185091709-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_007212.4(RNF2):c.218C>T(p.Ala73Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,762 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
RNF2
NM_007212.4 missense
NM_007212.4 missense
Scores
5
10
4
Clinical Significance
Conservation
PhyloP100: 7.39
Genes affected
RNF2 (HGNC:10061): (ring finger protein 2) Polycomb group (PcG) of proteins form the multiprotein complexes that are important for the transcription repression of various genes involved in development and cell proliferation. The protein encoded by this gene is one of the PcG proteins. It has been shown to interact with, and suppress the activity of, transcription factor CP2 (TFCP2/CP2). Studies of the mouse counterpart suggested the involvement of this gene in the specification of anterior-posterior axis, as well as in cell proliferation in early development. This protein was also found to interact with huntingtin interacting protein 2 (HIP2), an ubiquitin-conjugating enzyme, and possess ubiquitin ligase activity. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RNF2 | NM_007212.4 | c.218C>T | p.Ala73Val | missense_variant | 3/7 | ENST00000367510.8 | NP_009143.1 | |
RNF2 | XM_011509851.4 | c.218C>T | p.Ala73Val | missense_variant | 3/7 | XP_011508153.1 | ||
RNF2 | XM_011509852.3 | c.218C>T | p.Ala73Val | missense_variant | 3/7 | XP_011508154.1 | ||
RNF2 | XM_005245413.4 | c.71C>T | p.Ala24Val | missense_variant | 2/6 | XP_005245470.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RNF2 | ENST00000367510.8 | c.218C>T | p.Ala73Val | missense_variant | 3/7 | 1 | NM_007212.4 | ENSP00000356480 | P1 | |
RNF2 | ENST00000367509.8 | c.218C>T | p.Ala73Val | missense_variant | 3/6 | 2 | ENSP00000356479 | |||
RNF2 | ENST00000453650.2 | c.218C>T | p.Ala73Val | missense_variant | 3/5 | 5 | ENSP00000400722 | |||
RNF2 | ENST00000498201.1 | n.334C>T | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251368Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135856
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461762Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727174
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
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 | Mar 22, 2022 | The c.218C>T (p.A73V) alteration is located in exon 3 (coding exon 2) of the RNF2 gene. This alteration results from a C to T substitution at nucleotide position 218, causing the alanine (A) at amino acid position 73 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
B;.;.
Vest4
MutPred
Loss of catalytic residue at A73 (P = 0.0427);Loss of catalytic residue at A73 (P = 0.0427);Loss of catalytic residue at A73 (P = 0.0427);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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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