Variant 1-185100298-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_StrongBS2

The NM_007212.4(RNF2):c.1008A>G(p.Lys336=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000345 in 1,449,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

RNF2
NM_007212.4 synonymous

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.59

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 Likely_benign. Variant got -6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RNF2	NM_007212.4 linkuse as main transcript	c.1008A>G	p.Lys336=	synonymous_variant	7/7	ENST00000367510.8	NP_009143.1
RNF2	XM_011509851.4 linkuse as main transcript	c.1008A>G	p.Lys336=	synonymous_variant	7/7		XP_011508153.1
RNF2	XM_011509852.3 linkuse as main transcript	c.1008A>G	p.Lys336=	synonymous_variant	7/7		XP_011508154.1
RNF2	XM_005245413.4 linkuse as main transcript	c.861A>G	p.Lys287=	synonymous_variant	6/6		XP_005245470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF2	ENST00000367510.8 linkuse as main transcript	c.1008A>G	p.Lys336=	synonymous_variant	7/7	1	NM_007212.4	ENSP00000356480	P1	Q99496-1
RNF2	ENST00000367509.8 linkuse as main transcript	c.792A>G	p.Lys264=	synonymous_variant	6/6	2		ENSP00000356479		Q99496-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000345

AC:

AN:

1449718

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

720856

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:

0.00000451

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

RNF2-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 04, 2023

The RNF2 c.1008A>G variant is not predicted to result in an amino acid change (p.=). This variant is predicted to alter splicing based on available splicing prediction programs (Alamut Visual Plus v1.6.1). However, the use of computer prediction programs is not equivalent to functional evidence. 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over