Genetic Variant RNF2:p.Met220Val (chr1-185098265-ATG-GTT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is The variant received 2 classification points (ACMG Germline Pathogenicity v2019). PM2

The NM_007212.4(RNF2):c.658_660delATGinsGTT (p.Met220Val) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.M220?: Likely_benign (ClinVar VariationId 2500330, 1 star); p.M220V: Uncertain_significance (ClinVar VariationId 2319271, 1 star)

Frequency

Genomes: not found (cov: 32)

Consequence

RNF2
NM_007212.4 missense

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.58

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Luo-Schoch-Yamamoto syndrome
Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

RNF2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_007212.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Show applied only (1)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AD/XL gene) — PM2; Absent from gnomAD at well-covered site (MOI: AD/XL) (threshold 0.0001) — PM2 moderate.

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_007212.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	RNF2 NM_007212.4	MANE Select	c.658_660delATGinsGTT p.Met220Val	missense	N/A	Prot: NP_009143.1 UniProt: Q99496-1

RNF2 NM_007212.4

MANE Select

HGVSc / HGVSpc.658_660delATGinsGTTp.Met220Val

Exon rankN/A

missense

Prot: NP_009143.1UniProt: Q99496-1

Ensembl Transcripts

Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
RNF2 ENST00000367510.8	TSL:1MANE Select	c.658_660delATGinsGTT p.Met220Val	missense	N/A	Prot: ENSP00000356480.3 UniProt: Q99496-1
RNF2 ENST00000942958.1		c.685_687delATGinsGTT p.Met229Val	missense	N/A	Prot: ENSP00000613017.1 UniProt: A0ACI8U9C3
RNF2 ENST00000715230.1		c.658_660delATGinsGTT p.Met220Val	missense	N/A	Prot: ENSP00000520426.1 UniProt: Q99496-1

RNF2 ENST00000367510.8

TSL:1MANE Select

HGVSc / HGVSpc.658_660delATGinsGTTp.Met220Val

Exon rankN/A

missense

Prot: ENSP00000356480.3UniProt: Q99496-1

RNF2 ENST00000942958.1

HGVSc / HGVSpc.685_687delATGinsGTTp.Met229Val

Exon rankN/A

missense

Prot: ENSP00000613017.1UniProt: A0ACI8U9C3

RNF2 ENST00000715230.1

HGVSc / HGVSpc.658_660delATGinsGTTp.Met220Val

Exon rankN/A

missense

Prot: ENSP00000520426.1UniProt: Q99496-1

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 2 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Uncertain	4.6

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

MaveDB functional evidence ?

Publications

Other links and lift over

MaveDB functional evidence