17-80386817-G-GAGGGCAAACAGAGCGTGCAGC

Position:

• chr17-80386817-G-GAGGGCAAACAGAGCGTGCAGC

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP3

The NM_001256071.3(RNF213):​c.14850_14851insGGCAAACAGAGCGTGCAGCAG​(p.Glu4950_Phe4951insGlyLysGlnSerValGlnGln) variant causes a inframe insertion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF213 NM_001256071.3 inframe_insertion
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 8.75

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-AS1 (HGNC:54402): (RNF213 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001256071.3.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF213	NM_001256071.3	c.14850_14851insGGCAAACAGAGCGTGCAGCAG	p.Glu4950_Phe4951insGlyLysGlnSerValGlnGln	inframe_insertion	63/68	ENST00000582970.6	NP_001243000.2
RNF213-AS1	NR_029376.1	n.240+28111_240+28112insGCTGCACGCTCTGTTTGCCCT		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF213	ENST00000582970.6	c.14850_14851insGGCAAACAGAGCGTGCAGCAG	p.Glu4950_Phe4951insGlyLysGlnSerValGlnGln	inframe_insertion	63/68	1	NM_001256071.3	ENSP00000464087	P2
RNF213-AS1	ENST00000575034.5	n.190+28111_190+28112insGCTGCACGCTCTGTTTGCCCT		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Uncertain significance, no assertion criteria provided

research

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

Sep 08, 2014

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs797045188; hg19: chr17-78360617;