1-185098265-A-AC

Position:

• chr1-185098265-A-AC

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 10P and 2B. PVS1 PM2 BP6_Moderate

The NM_007212.4(RNF2):​c.658_659insC​(p.Met220ThrfsTer5) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF2 NM_007212.4 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.58

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 Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 1-185098265-A-AC is Benign according to our data. Variant chr1-185098265-A-AC is described in ClinVar as [Likely_benign]. Clinvar id is 2500330.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF2	NM_007212.4	c.658_659insC	p.Met220ThrfsTer5	frameshift_variant	5/7	ENST00000367510.8
RNF2	XM_005245413.4	c.511_512insC	p.Met171ThrfsTer5	frameshift_variant	4/6
RNF2	XM_011509851.4	c.658_659insC	p.Met220ThrfsTer5	frameshift_variant	5/7
RNF2	XM_011509852.3	c.658_659insC	p.Met220ThrfsTer5	frameshift_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF2	ENST00000367510.8	c.658_659insC	p.Met220ThrfsTer5	frameshift_variant	5/7	1	NM_007212.4	P1
RNF2	ENST00000367509.8	c.442_443insC	p.Met148ThrfsTer5	frameshift_variant	4/6	2
RNF2	ENST00000453650.2	c.658_659insC	p.Met220ThrfsTer5	frameshift_variant	5/5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Luo-Schoch-Yamamoto syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Institute of Human Genetics, University of Leipzig Medical Center

Jun 20, 2022

Criteria applied: BS1, PM2_SUP -

Computational scores

Source: dbNSFP v4.3

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: chr1-185067397;