Variant rs8940 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001233.5(CAV2):c.388C>G(p.Gln130Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,612,374 control chromosomes in the GnomAD database, including 24,883 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.17 ( 2305 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22578 hom. )

Consequence

CAV2
NM_001233.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.47

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014756322).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CAV2	NM_001233.5 linkuse as main transcript	c.388C>G	p.Gln130Glu	missense_variant	3/3	ENST00000222693.5	NP_001224.1
CAV2	NM_001206747.2 linkuse as main transcript	c.349C>G	p.Gln117Glu	missense_variant	3/3		NP_001193676.1
CAV2	NM_198212.3 linkuse as main transcript	c.200C>G	p.Ala67Gly	missense_variant	2/2		NP_937855.1
CAV2	NM_001206748.2 linkuse as main transcript	c.139C>G	p.Gln47Glu	missense_variant	2/2		NP_001193677.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAV2	ENST00000222693.5 linkuse as main transcript	c.388C>G	p.Gln130Glu	missense_variant	3/3	1	NM_001233.5	ENSP00000222693	P1	P51636-1

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25333

AN:

152036

Hom.:

2308

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.261

Gnomad EAS

AF:

0.0102

Gnomad SAS

AF:

0.179

Gnomad FIN

AF:

0.0690

Gnomad MID

AF:

0.242

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.182

GnomAD3 exomes

AF:

0.151

AC:

37877

AN:

251226

Hom.:

3518

AF XY:

0.157

AC XY:

21268

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.187

Gnomad AMR exome

AF:

0.106

Gnomad ASJ exome

AF:

0.268

Gnomad EAS exome

AF:

0.00772

Gnomad SAS exome

AF:

0.177

Gnomad FIN exome

AF:

0.0721

Gnomad NFE exome

AF:

0.178

Gnomad OTH exome

AF:

0.181

GnomAD4 exome

AF:

0.170

AC:

247598

AN:

1460220

Hom.:

22578

Cov.:

AF XY:

0.171

AC XY:

124405

AN XY:

726504

show subpopulations

Gnomad4 AFR exome

AF:

0.183

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.270

Gnomad4 EAS exome

AF:

0.00393

Gnomad4 SAS exome

AF:

0.182

Gnomad4 FIN exome

AF:

0.0748

Gnomad4 NFE exome

AF:

0.178

Gnomad4 OTH exome

AF:

0.172

GnomAD4 genome

AF:

0.167

AC:

25337

AN:

152154

Hom.:

2305

Cov.:

AF XY:

0.161

AC XY:

11988

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.187

Gnomad4 AMR

AF:

0.152

Gnomad4 ASJ

AF:

0.261

Gnomad4 EAS

AF:

0.0102

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.0690

Gnomad4 NFE

AF:

0.177

Gnomad4 OTH

AF:

0.179

Alfa

AF:

0.188

Hom.:

978

Bravo

AF:

0.174

TwinsUK

AF:

0.168

AC:

622

ALSPAC

AF:

0.182

AC:

702

ESP6500AA

AF:

0.192

AC:

845

ESP6500EA

AF:

0.194

AC:

1670

ExAC

AF:

0.153

AC:

18571

Asia WGS

AF:

0.0820

AC:

287

AN:

3478

EpiCase

AF:

0.190

EpiControl

AF:

0.195

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.40

MetaRNN

Benign

0.0015

MetaSVM

Benign

-0.98

MutationTaster

Benign

0.0000068

P;P

PROVEAN

Benign

-0.61

REVEL

Benign

0.25

Sift

Benign

0.12

Sift4G

Benign

0.24

Polyphen

1.0

Vest4

0.32

ClinPred

0.017

GERP RS

5.9

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over