1-185098341-C-T

Variant summary

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

The NM_007212.4(RNF2):​c.734C>T​(p.Thr245Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,172 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

Scores

4
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.46
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 UniProt
RNF2NM_007212.4 linkuse as main transcriptc.734C>T p.Thr245Met missense_variant 5/7 ENST00000367510.8
RNF2XM_011509851.4 linkuse as main transcriptc.734C>T p.Thr245Met missense_variant 5/7
RNF2XM_011509852.3 linkuse as main transcriptc.734C>T p.Thr245Met missense_variant 5/7
RNF2XM_005245413.4 linkuse as main transcriptc.587C>T p.Thr196Met missense_variant 4/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNF2ENST00000367510.8 linkuse as main transcriptc.734C>T p.Thr245Met missense_variant 5/71 NM_007212.4 P1Q99496-1
RNF2ENST00000367509.8 linkuse as main transcriptc.518C>T p.Thr173Met missense_variant 4/62 Q99496-2
RNF2ENST00000453650.2 linkuse as main transcriptc.734C>T p.Thr245Met missense_variant 5/55

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461172
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726780
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenNov 01, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.10
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.53
D;.;.
Eigen
Uncertain
0.64
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.88
D;D;D
M_CAP
Uncertain
0.14
D
MetaRNN
Uncertain
0.63
D;D;D
MetaSVM
Uncertain
0.42
D
MutationAssessor
Benign
2.0
M;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-1.2
N;N;N
REVEL
Uncertain
0.56
Sift
Uncertain
0.024
D;D;D
Sift4G
Benign
0.093
T;D;D
Polyphen
0.98
D;.;.
Vest4
0.68
MutPred
0.35
Loss of methylation at K249 (P = 0.0707);.;Loss of methylation at K249 (P = 0.0707);
MVP
0.82
MPC
1.6
ClinPred
0.83
D
GERP RS
5.6
Varity_R
0.22
gMVP
0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1404122501; hg19: chr1-185067473; COSMIC: COSV100835834; API