Genetic Variant CAV2:c.338+23G>T (chr7-116500470-G-T) – 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.338+23G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 1,600,476 control chromosomes in the GnomAD database, including 209,530 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 0.49 ( 18909 hom., cov: 32)

Exomes 𝑓: 0.51 ( 190621 hom. )

Consequence

CAV2
NM_001233.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.526

Publications

22 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 (BayesDel_noAF=-0.73).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 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	Effect	Exon Rank	Protein	UniProt
CAV2	NM_001233.5	MANE Select	c.338+23G>T	intron	N/A	NP_001224.1	Q53X57
CAV2	NM_001206747.2		c.299+23G>T	intron	N/A	NP_001193676.1	P51636-2
CAV2	NM_198212.3		c.150+539G>T	intron	N/A	NP_937855.1	P51636-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CAV2	ENST00000222693.5	TSL:1 MANE Select	c.338+23G>T	intron	N/A	ENSP00000222693.4	P51636-1
CAV2	ENST00000343213.2	TSL:1	c.150+539G>T	intron	N/A	ENSP00000345679.2	P51636-3
CAV2	ENST00000462876.5	TSL:1	n.1598+23G>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.491

AC:

74505

AN:

151836

Hom.:

18887

Cov.:

show subpopulations

Gnomad AFR

AF:

0.389

Gnomad AMI

AF:

0.424

Gnomad AMR

AF:

0.561

Gnomad ASJ

AF:

0.486

Gnomad EAS

AF:

0.773

Gnomad SAS

AF:

0.548

Gnomad FIN

AF:

0.568

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.501

Gnomad OTH

AF:

0.496

GnomAD2 exomes

AF:

0.541

AC:

130712

AN:

241486

AF XY:

0.539

show subpopulations

Gnomad AFR exome

AF:

0.389

Gnomad AMR exome

AF:

0.620

Gnomad ASJ exome

AF:

0.482

Gnomad EAS exome

AF:

0.786

Gnomad FIN exome

AF:

0.558

Gnomad NFE exome

AF:

0.499

Gnomad OTH exome

AF:

0.523

GnomAD4 exome

AF:

0.509

AC:

737744

AN:

1448522

Hom.:

190621

Cov.:

AF XY:

0.510

AC XY:

366887

AN XY:

719596

show subpopulations

African (AFR)

AF:

0.385

AC:

12797

AN:

33266

American (AMR)

AF:

0.612

AC:

27051

AN:

44166

Ashkenazi Jewish (ASJ)

AF:

0.476

AC:

12032

AN:

25254

East Asian (EAS)

AF:

0.759

AC:

30001

AN:

39530

South Asian (SAS)

AF:

0.536

AC:

45173

AN:

84298

European-Finnish (FIN)

AF:

0.555

AC:

29329

AN:

52810

Middle Eastern (MID)

AF:

0.508

AC:

2595

AN:

5110

European-Non Finnish (NFE)

AF:

0.496

AC:

547764

AN:

1104274

Other (OTH)

AF:

0.518

AC:

31002

AN:

59814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

17063

34126

51189

68252

85315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16162

32324

48486

64648

80810

<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:

0.491

AC:

74568

AN:

151954

Hom.:

18909

Cov.:

AF XY:

0.499

AC XY:

37048

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.388

AC:

16089

AN:

41422

American (AMR)

AF:

0.561

AC:

8570

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.486

AC:

1686

AN:

3470

East Asian (EAS)

AF:

0.773

AC:

3990

AN:

5162

South Asian (SAS)

AF:

0.548

AC:

2640

AN:

4818

European-Finnish (FIN)

AF:

0.568

AC:

5979

AN:

10530

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.501

AC:

34040

AN:

67968

Other (OTH)

AF:

0.501

AC:

1056

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1849

3698

5546

7395

9244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

670

1340

2010

2680

3350

<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:

0.465

Hom.:

5431

Bravo

AF:

0.483

Asia WGS

AF:

0.680

AC:

2360

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.9

(source)

DANN

Benign

0.87

PhyloP100

-0.53

Mutation Taster

=100/0

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