1-185091737-T-G

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

Scores

4
8
7
Splicing: ADA: 0.0004431
2

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 0.773
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 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 UniProt
RNF2NM_007212.4 linkuse as main transcriptc.246T>G p.Ser82Arg missense_variant, splice_region_variant 3/7 ENST00000367510.8
RNF2XM_011509851.4 linkuse as main transcriptc.246T>G p.Ser82Arg missense_variant, splice_region_variant 3/7
RNF2XM_011509852.3 linkuse as main transcriptc.246T>G p.Ser82Arg missense_variant, splice_region_variant 3/7
RNF2XM_005245413.4 linkuse as main transcriptc.99T>G p.Ser33Arg missense_variant, splice_region_variant 2/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNF2ENST00000367510.8 linkuse as main transcriptc.246T>G p.Ser82Arg missense_variant, splice_region_variant 3/71 NM_007212.4 P1Q99496-1
RNF2ENST00000367509.8 linkuse as main transcriptc.246T>G p.Ser82Arg missense_variant, splice_region_variant 3/62 Q99496-2
RNF2ENST00000453650.2 linkuse as main transcriptc.246T>G p.Ser82Arg missense_variant, splice_region_variant 3/55
RNF2ENST00000498201.1 linkuse as main transcriptn.362T>G non_coding_transcript_exon_variant 3/32

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
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 providedliterature onlyOMIMAug 19, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.46
T;.;.
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.11
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Uncertain
0.48
T;T;T
MetaSVM
Benign
-0.38
T
MutationAssessor
Benign
0.96
L;L;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.90
D
PROVEAN
Pathogenic
-4.7
D;D;D
REVEL
Uncertain
0.59
Sift
Benign
0.037
D;T;T
Sift4G
Benign
0.27
T;D;T
Polyphen
1.0
D;.;.
Vest4
0.71
MutPred
0.46
Gain of MoRF binding (P = 0.0302);Gain of MoRF binding (P = 0.0302);Gain of MoRF binding (P = 0.0302);
MVP
0.91
MPC
1.0
ClinPred
0.91
D
GERP RS
2.6
Varity_R
0.75
gMVP
0.92

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00044
dbscSNV1_RF
Benign
0.20
SpliceAI score (max)
0.040
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: chr1-185060869; API