7-116506020-CAG-GAA

Variant names:

• chr7-116506020-CAG-GAA
• NM_001233.5:c.388_390delCAGinsGAA
• CAV2 p.Gln130Glu

Variant summary

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

The NM_001233.5(CAV2):​c.388_390delCAGinsGAA​(p.Gln130Glu) variant causes a missense 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: CAV2 NM_001233.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.35
• Publications: 0 publications found

Genes affected

CAV2 (HGNC:1528): (caveolin 2) The protein encoded by this gene is a major component of the inner surface of caveolae, small invaginations of the plasma membrane, and is involved in essential cellular functions, including signal transduction, lipid metabolism, cellular growth control and apoptosis. This protein may function as a tumor suppressor. This gene and related family member (CAV1) are located next to each other on chromosome 7, and express colocalizing proteins that form a stable hetero-oligomeric complex. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. Additional isoforms resulting from the use of alternate in-frame translation initiation codons have also been described, and shown to have preferential localization in the cell (PMID:11238462). [provided by RefSeq, May 2011]

CAV2 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001233.5. 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
	CAV2	NM_001233.5	MANE Select	c.388_390delCAGinsGAA	p.Gln130Glu	missense	N/A	NP_001224.1	Q53X57
	CAV2	NM_001206747.2		c.349_351delCAGinsGAA	p.Gln117Glu	missense	N/A	NP_001193676.1	P51636-2
	CAV2	NM_198212.3		c.200_202delCAGinsGAA	p.AlaAsp67GlyAsn	missense	N/A	NP_937855.1	P51636-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAV2	ENST00000222693.5	TSL:1 MANE Select	c.388_390delCAGinsGAA	p.Gln130Glu	missense	N/A	ENSP00000222693.4	P51636-1
	CAV2	ENST00000343213.2	TSL:1	c.200_202delCAGinsGAA	p.AlaAsp67GlyAsn	missense	N/A	ENSP00000345679.2	P51636-3
	CAV2	ENST00000462876.5	TSL:1	n.1773_1775delCAGinsGAA		non_coding_transcript_exon	Exon 14 of 14

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		7.3

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: chr7-116146074;