1-185100285-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007212.4(RNF2):​c.995C>A​(p.Thr332Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

RNF2
NM_007212.4 missense

Scores

4
8
7

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 7.41
Variant links:
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]

Genome browser will be placed here

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
RNF2NM_007212.4 linkuse as main transcriptc.995C>A p.Thr332Lys missense_variant 7/7 ENST00000367510.8 NP_009143.1
RNF2XM_011509851.4 linkuse as main transcriptc.995C>A p.Thr332Lys missense_variant 7/7 XP_011508153.1
RNF2XM_011509852.3 linkuse as main transcriptc.995C>A p.Thr332Lys missense_variant 7/7 XP_011508154.1
RNF2XM_005245413.4 linkuse as main transcriptc.848C>A p.Thr283Lys missense_variant 6/6 XP_005245470.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RNF2ENST00000367510.8 linkuse as main transcriptc.995C>A p.Thr332Lys missense_variant 7/71 NM_007212.4 ENSP00000356480 P1Q99496-1
RNF2ENST00000367509.8 linkuse as main transcriptc.779C>A p.Thr260Lys missense_variant 6/62 ENSP00000356479 Q99496-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

RNF2-related disorder Uncertain:1
Uncertain significance, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesOct 30, 2023The RNF2 c.995C>A variant is predicted to result in the amino acid substitution p.Thr332Lys. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.85
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Pathogenic
0.14
CADD
Benign
21
DANN
Benign
0.97
DEOGEN2
Benign
0.27
T;.
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Benign
0.058
D
MetaRNN
Uncertain
0.54
D;D
MetaSVM
Uncertain
-0.040
T
MutationAssessor
Benign
0.84
L;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
1.0
N;N
REVEL
Uncertain
0.47
Sift
Uncertain
0.0080
D;D
Sift4G
Benign
0.44
T;T
Polyphen
0.73
P;.
Vest4
0.64
MutPred
0.28
Gain of methylation at T332 (P = 0.0019);.;
MVP
0.89
MPC
1.1
ClinPred
0.94
D
GERP RS
6.1
Varity_R
0.60
gMVP
0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-185069417; API