Genetic Variant NM_001233.5:c.388C>G (chr7-116506020-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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.

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

Publications

44 publications found

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 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

CAV2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CAV2	NM_001233.5	MANE Select	c.388C>G	p.Gln130Glu	missense	Exon 3 of 3	NP_001224.1
CAV2	NM_001206747.2		c.349C>G	p.Gln117Glu	missense	Exon 3 of 3	NP_001193676.1
CAV2	NM_198212.3		c.200C>G	p.Ala67Gly	missense	Exon 2 of 2	NP_937855.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CAV2	ENST00000222693.5	TSL:1 MANE Select	c.388C>G	p.Gln130Glu	missense	Exon 3 of 3	ENSP00000222693.4
CAV2	ENST00000343213.2	TSL:1	c.200C>G	p.Ala67Gly	missense	Exon 2 of 2	ENSP00000345679.2
CAV2	ENST00000462876.5	TSL:1	n.1773C>G		non_coding_transcript_exon	Exon 14 of 14

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

GnomAD2 exomes

AF:

0.151

AC:

37877

AN:

251226

AF XY:

0.157

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 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

African (AFR)

AF:

0.183

AC:

6122

AN:

33452

American (AMR)

AF:

0.111

AC:

4942

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.270

AC:

7059

AN:

26124

East Asian (EAS)

AF:

0.00393

AC:

156

AN:

39692

South Asian (SAS)

AF:

0.182

AC:

15707

AN:

86190

European-Finnish (FIN)

AF:

0.0748

AC:

3998

AN:

53414

Middle Eastern (MID)

AF:

0.231

AC:

1332

AN:

5766

European-Non Finnish (NFE)

AF:

0.178

AC:

197934

AN:

1110532

Other (OTH)

AF:

0.172

AC:

10348

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

9471

18941

28412

37882

47353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6854

13708

20562

27416

34270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.167

AC:

25337

AN:

152154

Hom.:

2305

Cov.:

AF XY:

0.161

AC XY:

11988

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.187

AC:

7777

AN:

41498

American (AMR)

AF:

0.152

AC:

2321

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

904

AN:

3470

East Asian (EAS)

AF:

0.0102

AC:

AN:

5188

South Asian (SAS)

AF:

0.179

AC:

861

AN:

4812

European-Finnish (FIN)

AF:

0.0690

AC:

732

AN:

10606

Middle Eastern (MID)

AF:

0.236

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.177

AC:

12021

AN:

67990

Other (OTH)

AF:

0.179

AC:

378

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1063

2127

3190

4254

5317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

274

548

822

1096

1370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

(source)

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

PhyloP100

3.5

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

Varity_R

0.52

Mutation Taster

=60/40

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over