Genetic Variant ENST00000462876.5:n.470-6552G>T (chr7-116330568-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 ENST00000462876.5(CAV2):n.470-6552G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,994 control chromosomes in the GnomAD database, including 8,735 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 0.33 ( 8735 hom., cov: 32)

Consequence

CAV2
ENST00000462876.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.147

Publications

6 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:

ENSG00000237813 (HGNC:40129):

ENSG00000237813 links:

LOC105375463 (HGNC:):

LOC105375463 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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
LOC105375463	XR_001745329.2 link	n.966-6552G>T	intron_variant	Intron 5 of 5
LOC105375463	XR_001745332.2 link	n.827-6552G>T	intron_variant	Intron 6 of 6
LOC105375463	XR_001745335.2 link	n.565-6552G>T	intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CAV2	ENST00000462876.5 link	n.470-6552G>T	intron_variant	Intron 4 of 13	1
CAV2	ENST00000467035.5 link	n.295-9255G>T	intron_variant	Intron 3 of 8	1
CAV2	ENST00000472470.5 link	n.241+40518G>T	intron_variant	Intron 2 of 5	1

Frequencies

GnomAD3 genomes

AF:

0.328

AC:

49752

AN:

151876

Hom.:

8735

Cov.:

show subpopulations

Gnomad AFR

AF:

0.420

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.410

Gnomad EAS

AF:

0.0688

Gnomad SAS

AF:

0.284

Gnomad FIN

AF:

0.228

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.324

Gnomad OTH

AF:

0.341

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

GnomAD4 genome

AF:

0.327

AC:

49763

AN:

151994

Hom.:

8735

Cov.:

AF XY:

0.319

AC XY:

23681

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.420

AC:

17388

AN:

41424

American (AMR)

AF:

0.248

AC:

3789

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.410

AC:

1420

AN:

3466

East Asian (EAS)

AF:

0.0690

AC:

357

AN:

5176

South Asian (SAS)

AF:

0.283

AC:

1364

AN:

4812

European-Finnish (FIN)

AF:

0.228

AC:

2413

AN:

10576

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.324

AC:

21995

AN:

67954

Other (OTH)

AF:

0.337

AC:

712

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1686

3372

5058

6744

8430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

498

996

1494

1992

2490

<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:

0.328

Hom.:

10913

Bravo

AF:

0.331

Asia WGS

AF:

0.183

AC:

638

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.73

(source)

DANN

Benign

0.44

PhyloP100

-0.15

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over