1-185100285-C-A

Position:

• chr1-185100285-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
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.41

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]

ACMG classification

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
RNF2	NM_007212.4	c.995C>A	p.Thr332Lys	missense_variant	7/7	ENST00000367510.8
RNF2	XM_011509851.4	c.995C>A	p.Thr332Lys	missense_variant	7/7
RNF2	XM_011509852.3	c.995C>A	p.Thr332Lys	missense_variant	7/7
RNF2	XM_005245413.4	c.848C>A	p.Thr283Lys	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF2	ENST00000367510.8	c.995C>A	p.Thr332Lys	missense_variant	7/7	1	NM_007212.4	P1
RNF2	ENST00000367509.8	c.779C>A	p.Thr260Lys	missense_variant	6/6	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

Submissions by phenotype

RNF2-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2023

The 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;