Genetic Variant CAV2:n.1007-14880G>A (chr7-116482889-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NR_188009.1(CAV2-DT):n.178C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,974 control chromosomes in the GnomAD database, including 20,044 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 0.51 ( 20039 hom., cov: 31)

Exomes 𝑓: 0.43 ( 5 hom. )

Consequence

CAV2-DT
NR_188009.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.458

Publications

9 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:

CAV2-DT (HGNC:40129):

CAV2-DT links:

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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=-0.88).

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: NR_188009.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
CAV2-DT	NR_188009.1	n.178C>T	non_coding_transcript_exon	Exon 2 of 4
CAV2-DT	NR_188011.1	n.178C>T	non_coding_transcript_exon	Exon 2 of 5
CAV2-DT	NR_188010.1	n.163+16465C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CAV2	ENST00000462876.5	TSL:1	n.1007-14880G>A	intron	N/A
CAV2	ENST00000467035.5	TSL:1	n.753-14880G>A	intron	N/A
CAV2	ENST00000472470.5	TSL:1	n.407-14880G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.506

AC:

76851

AN:

151812

Hom.:

20022

Cov.:

show subpopulations

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.531

Gnomad AMR

AF:

0.575

Gnomad ASJ

AF:

0.490

Gnomad EAS

AF:

0.774

Gnomad SAS

AF:

0.555

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.518

Gnomad OTH

AF:

0.516

GnomAD4 exome

AF:

0.432

AC:

AN:

Hom.:

Cov.:

AF XY:

0.471

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.421

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.506

AC:

76897

AN:

151930

Hom.:

20039

Cov.:

AF XY:

0.513

AC XY:

38076

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.406

AC:

16817

AN:

41406

American (AMR)

AF:

0.576

AC:

8799

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.490

AC:

1697

AN:

3464

East Asian (EAS)

AF:

0.773

AC:

3984

AN:

5154

South Asian (SAS)

AF:

0.555

AC:

2666

AN:

4804

European-Finnish (FIN)

AF:

0.570

AC:

6025

AN:

10566

Middle Eastern (MID)

AF:

0.452

AC:

133

AN:

294

European-Non Finnish (NFE)

AF:

0.518

AC:

35197

AN:

67952

Other (OTH)

AF:

0.520

AC:

1095

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1911

3822

5732

7643

9554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

684

1368

2052

2736

3420

<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:

0.501

Hom.:

12093

Bravo

AF:

0.499

Asia WGS

AF:

0.684

AC:

2372

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.9

(source)

DANN

Benign

0.72

PhyloP100

0.46

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over