1-185091737-T-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_007212.4(RNF2):c.246T>G(p.Ser82Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
RNF2
NM_007212.4 missense, splice_region
NM_007212.4 missense, splice_region
Scores
4
8
7
Splicing: ADA: 0.0004431
2
Clinical Significance
Conservation
PhyloP100: 0.773
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 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-185091737-T-G is Pathogenic according to our data. Variant chr1-185091737-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 1189036.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RNF2 | NM_007212.4 | c.246T>G | p.Ser82Arg | missense_variant, splice_region_variant | 3/7 | ENST00000367510.8 | NP_009143.1 | |
RNF2 | XM_011509851.4 | c.246T>G | p.Ser82Arg | missense_variant, splice_region_variant | 3/7 | XP_011508153.1 | ||
RNF2 | XM_011509852.3 | c.246T>G | p.Ser82Arg | missense_variant, splice_region_variant | 3/7 | XP_011508154.1 | ||
RNF2 | XM_005245413.4 | c.99T>G | p.Ser33Arg | missense_variant, splice_region_variant | 2/6 | XP_005245470.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RNF2 | ENST00000367510.8 | c.246T>G | p.Ser82Arg | missense_variant, splice_region_variant | 3/7 | 1 | NM_007212.4 | ENSP00000356480 | P1 | |
RNF2 | ENST00000367509.8 | c.246T>G | p.Ser82Arg | missense_variant, splice_region_variant | 3/6 | 2 | ENSP00000356479 | |||
RNF2 | ENST00000453650.2 | c.246T>G | p.Ser82Arg | missense_variant, splice_region_variant | 3/5 | 5 | ENSP00000400722 | |||
RNF2 | ENST00000498201.1 | n.362T>G | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Luo-Schoch-Yamamoto syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 19, 2021 | - - |
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
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Benign
D;T;T
Sift4G
Benign
T;D;T
Polyphen
D;.;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0302);Gain of MoRF binding (P = 0.0302);Gain of MoRF binding (P = 0.0302);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.