chr17-80294832-TGCC-T

Variant names:

• chr17-80294832-TGCC-T
• rs797045186
• NM_001256071.3:c.1587_1589delCGC

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_001256071.3(RNF213):​c.1587_1589delCGC​(p.Ala530del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars). Synonymous variant affecting the same amino acid position (i.e. A529A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF213 NM_001256071.3 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 6.05
• Publications: 2 publications found

Genes affected

RNF213 (HGNC:14539): (ring finger protein 213) This gene encodes a protein containing a C3HC4-type RING finger domain, which is a specialized type of Zn-finger that binds two atoms of zinc and is thought to be involved in mediating protein-protein interactions. The protein also contains an AAA domain, which is associated with ATPase activity. This gene is a susceptibility gene for Moyamoya disease, a vascular disorder of intracranial arteries. This gene is also a translocation partner in anaplastic large cell lymphoma and inflammatory myofibroblastic tumor cases, where a t(2;17)(p23;q25) translocation has been identified with the anaplastic lymphoma kinase (ALK) gene on chromosome 2, and a t(8;17)(q24;q25) translocation has been identified with the MYC gene on chromosome 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]

RNF213 Gene-Disease associations (from GenCC):

• Moyamoya disease 2

  Inheritance: AD, AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001256071.3. Strenght limited to Supporting due to length of the change: 1aa.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256071.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF213	NM_001256071.3	MANE Select	c.1587_1589delCGC	p.Ala530del	disruptive_inframe_deletion	Exon 9 of 68	NP_001243000.2
	RNF213	NM_001410195.1		c.1734_1736delCGC	p.Ala579del	disruptive_inframe_deletion	Exon 10 of 69	NP_001397124.1
	RNF213	NM_020914.5		c.1734_1736delCGC	p.Ala579del	disruptive_inframe_deletion	Exon 10 of 69	NP_065965.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF213	ENST00000582970.6	TSL:1 MANE Select	c.1587_1589delCGC	p.Ala530del	disruptive_inframe_deletion	Exon 9 of 68	ENSP00000464087.1
	RNF213	ENST00000319921.4	TSL:1	c.1587_1589delCGC	p.Ala530del	disruptive_inframe_deletion	Exon 9 of 17	ENSP00000324392.4
	RNF213	ENST00000559070.5	TSL:1	n.1182_1184delCGC		non_coding_transcript_exon	Exon 6 of 20

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Moyamoya disease 2 Uncertain:1

Sep 08, 2014

Department of Internal Medicine, University of Texas Health Science Center at Houston

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.0

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

Other links and lift over

dbSNP: rs797045186; hg19: chr17-78268631;