dbSNP rs148949992: RNF2:p.Asn322Lys (chr1-185100256-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_007212.4(RNF2):c.966C>A(p.Asn322Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,612,286 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N322N) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RNF2
NM_007212.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.77

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]

RNF2 links:

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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 rank	MANE	Protein	UniProt
RNF2	NM_007212.4 link	c.966C>A	p.Asn322Lys	missense_variant	Exon 7 of 7	ENST00000367510.8	NP_009143.1
RNF2	XM_011509851.4 link	c.966C>A	p.Asn322Lys	missense_variant	Exon 7 of 7		XP_011508153.1	Q99496-1
RNF2	XM_011509852.3 link	c.966C>A	p.Asn322Lys	missense_variant	Exon 7 of 7		XP_011508154.1	Q99496-1
RNF2	XM_005245413.4 link	c.819C>A	p.Asn273Lys	missense_variant	Exon 6 of 6		XP_005245470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF2	ENST00000367510.8 link	c.966C>A	p.Asn322Lys	missense_variant	Exon 7 of 7	1	NM_007212.4	ENSP00000356480.3		Q99496-1
RNF2	ENST00000367509.8 link	c.750C>A	p.Asn250Lys	missense_variant	Exon 6 of 6	2		ENSP00000356479.4		Q99496-2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460248

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726334

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

AF:

0.00000658

AC:

AN:

152038

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.072

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.75

D;.

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.072

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.80

T;T

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.73

D;D

MetaSVM

Uncertain

-0.18

MutationAssessor

Benign

1.6

L;.

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-4.0

D;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.015

D;D

Sift4G

Uncertain

0.046

D;D

Polyphen

0.71

P;.

Vest4

0.73

MutPred

0.42

Gain of methylation at N322 (P = 0.0022);.;

MVP

0.81

MPC

2.1

ClinPred

0.98

GERP RS

4.1

Varity_R

0.81

gMVP

0.54

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over