8-23007710-CGG-AGA

Variant names:

• chr8-23007710-CGG-AGA
• NM_015178.3:c.1465_1467delCGGinsAGA
• RHOBTB2 p.490

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_015178.3(RHOBTB2):​c.1465_1467delCGGinsAGA​(p.490) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RHOBTB2 NM_015178.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.15
• Publications: 0 publications found

Genes affected

RHOBTB2 (HGNC:18756): (Rho related BTB domain containing 2) The protein encoded by this gene is a small Rho GTPase and a candidate tumor suppressor. The encoded protein interacts with the cullin-3 protein, a ubiquitin E3 ligase necessary for mitotic cell division. This protein inhibits the growth and spread of some types of breast cancer. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

RHOBTB2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR, AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 64

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

RHOBTB2-AS1 (HGNC:58239):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015178.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOBTB2	NM_015178.3	MANE Select	c.1465_1467delCGGinsAGA	p.490	synonymous	N/A	NP_055993.2	Q9BYZ6-1
	RHOBTB2	NM_001160036.2		c.1531_1533delCGGinsAGA	p.512	synonymous	N/A	NP_001153508.1	Q9BYZ6-2
	RHOBTB2	NM_001160037.2		c.1486_1488delCGGinsAGA	p.497	synonymous	N/A	NP_001153509.1	Q9BYZ6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOBTB2	ENST00000251822.7	TSL:1 MANE Select	c.1465_1467delCGGinsAGA	p.490	synonymous	N/A	ENSP00000251822.7	Q9BYZ6-1
	RHOBTB2	ENST00000519685.5	TSL:1	c.1531_1533delCGGinsAGA	p.512	synonymous	N/A	ENSP00000427926.1	Q9BYZ6-2
	RHOBTB2-AS1	ENST00000502083.2	TSL:1	n.614_616delCCGinsTCT		non_coding_transcript_exon	Exon 2 of 2

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.2

Splicing

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.

Other links and lift over

hg19: chr8-22865223;