8-142917751-CC-TT

Variant names:

• chr8-142917751-CC-TT
• NM_000498.3:c.89_90delGGinsAA
• CYP11B2 p.Arg30Gln

Variant summary

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

The NM_000498.3(CYP11B2):​c.89_90delGGinsAA​(p.Arg30Gln) variant causes a missense change involving the alteration of a non-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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R30W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CYP11B2 NM_000498.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288
• Publications: 0 publications found

Genes affected

CYP11B2 (HGNC:2592): (cytochrome P450 family 11 subfamily B member 2) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the mitochondrial inner membrane. The enzyme has steroid 18-hydroxylase activity to synthesize aldosterone and 18-oxocortisol as well as steroid 11 beta-hydroxylase activity. Mutations in this gene cause corticosterone methyl oxidase deficiency. [provided by RefSeq, Jul 2008]

CYP11B2 Gene-Disease associations (from GenCC):

• familial hyperreninemic hypoaldosteronism type 2

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• corticosterone methyloxidase type 2 deficiency

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• corticosterone methyloxidase type 1 deficiency

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• familial hypoaldosteronism

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000498.3. 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
	CYP11B2	NM_000498.3	MANE Select	c.89_90delGGinsAA	p.Arg30Gln	missense	N/A	NP_000489.3	P19099

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP11B2	ENST00000323110.2	TSL:1 MANE Select	c.89_90delGGinsAA	p.Arg30Gln	missense	N/A	ENSP00000325822.2	P19099
	CYP11B2	ENST00000945895.1		c.89_90delGGinsAA	p.Arg30Gln	missense	N/A	ENSP00000615954.1
	CYP11B2	ENST00000945896.1		c.89_90delGGinsAA	p.Arg30Gln	missense	N/A	ENSP00000615955.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.29

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: chr8-143999167;