Variant chr7-116506073-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000343213.2(CAV2):c.253C>T(p.Arg85Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,613,866 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R85H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0023 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 72 hom. )

Consequence

CAV2
ENST00000343213.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.566

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013436079).

BP6

Variant 7-116506073-C-T is Benign according to our data. Variant chr7-116506073-C-T is described in ClinVar as [Benign]. Clinvar id is 779921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CAV2	NM_001233.5 linkuse as main transcript	c.441C>T	p.Ser147=	synonymous_variant	3/3	ENST00000222693.5
CAV2	NM_198212.3 linkuse as main transcript	c.253C>T	p.Arg85Cys	missense_variant	2/2
CAV2	NM_001206747.2 linkuse as main transcript	c.402C>T	p.Ser134=	synonymous_variant	3/3
CAV2	NM_001206748.2 linkuse as main transcript	c.192C>T	p.Ser64=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAV2	ENST00000222693.5 linkuse as main transcript	c.441C>T	p.Ser147=	synonymous_variant	3/3	1	NM_001233.5	P1	P51636-1

Frequencies

GnomAD3 genomes

AF:

0.00231

AC:

351

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0559

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00475

AC:

1195

AN:

251432

Hom.:

AF XY:

0.00435

AC XY:

591

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0606

Gnomad SAS exome

AF:

0.00154

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00169

AC:

2476

AN:

1461636

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

1204

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0513

Gnomad4 SAS exome

AF:

0.00150

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000432

Gnomad4 OTH exome

AF:

0.00407

GnomAD4 genome

AF:

0.00231

AC:

351

AN:

152230

Hom.:

Cov.:

AF XY:

0.00253

AC XY:

188

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0560

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00522

Alfa

AF:

0.00257

Hom.:

Bravo

AF:

0.00277

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00436

AC:

529

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.34

CADD

Benign

5.4

DANN

Benign

0.84

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.43

MetaRNN

Benign

0.0013

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;N

PROVEAN

Benign

0.58

REVEL

Benign

0.088

Sift

Benign

0.074

Sift4G

Benign

0.20

Polyphen

0.0

Vest4

0.15

MVP

0.39

ClinPred

0.0031

GERP RS

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over