dbSNP rs17138767: CAV2:n.1007-146A>G (chr7-116497623-A-G) – 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.1007-146A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0721 in 152,276 control chromosomes in the GnomAD database, including 610 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 0.072 ( 610 hom., cov: 32)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

CAV2
ENST00000462876.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.16

Publications

5 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:

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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
CAV2-DT	NR_188009.1 link	n.163+1731T>C	intron_variant	Intron 1 of 3
CAV2-DT	NR_188010.1 link	n.163+1731T>C	intron_variant	Intron 1 of 3
CAV2-DT	NR_188011.1 link	n.163+1731T>C	intron_variant	Intron 1 of 4
CAV2-DT	NR_188012.1 link	n.163+1731T>C	intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CAV2	ENST00000462876.5 link	n.1007-146A>G	intron_variant	Intron 8 of 13	1
CAV2	ENST00000467035.5 link	n.753-146A>G	intron_variant	Intron 6 of 8	1
CAV2	ENST00000472470.5 link	n.407-146A>G	intron_variant	Intron 3 of 5	1

Frequencies

GnomAD3 genomes

AF:

0.0722

AC:

10985

AN:

152158

Hom.:

612

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0292

Gnomad AMI

AF:

0.0407

Gnomad AMR

AF:

0.0827

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.162

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0727

Gnomad OTH

AF:

0.0544

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0721

AC:

10982

AN:

152274

Hom.:

610

Cov.:

AF XY:

0.0774

AC XY:

5761

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0292

AC:

1213

AN:

41580

American (AMR)

AF:

0.0827

AC:

1266

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0343

AC:

119

AN:

3468

East Asian (EAS)

AF:

0.162

AC:

836

AN:

5174

South Asian (SAS)

AF:

0.121

AC:

581

AN:

4820

European-Finnish (FIN)

AF:

0.176

AC:

1865

AN:

10592

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0727

AC:

4943

AN:

68020

Other (OTH)

AF:

0.0534

AC:

113

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

506

1011

1517

2022

2528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<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:

0.0710

Hom.:

121

Bravo

AF:

0.0649

Asia WGS

AF:

0.111

AC:

386

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

9.4

(source)

DANN

Benign

0.73

PhyloP100

1.2

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