dbSNP rs115736105: CAVIN2:p.His337Tyr (chr2-191836192-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004657.6(CAVIN2):c.1009C>T(p.His337Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,614,118 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

CAVIN2
NM_004657.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.95

Variant links:

Genes affected

CAVIN2 (HGNC:10690): (caveolae associated protein 2) This gene encodes a calcium-independent phospholipid-binding protein whose expression increases in serum-starved cells. This protein is a substrate for protein kinase C (PKC) phosphorylation and recruits polymerase I and transcript release factor (PTRF) to caveolae. Removal of this protein causes caveolae loss and its over-expression results in caveolae deformation and membrane tubulation.[provided by RefSeq, Sep 2009]

CAVIN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0066559017).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAVIN2	NM_004657.6 link	c.1009C>T	p.His337Tyr	missense_variant	Exon 2 of 2	ENST00000304141.5	NP_004648.1	O95810

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAVIN2	ENST00000304141.5 link	c.1009C>T	p.His337Tyr	missense_variant	Exon 2 of 2	1	NM_004657.6	ENSP00000305675.4		O95810

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

235

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00550

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000387

AC:

AN:

250926

Hom.:

AF XY:

0.000324

AC XY:

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.00561

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000133

AC:

194

AN:

1461856

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00490

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.00154

AC:

235

AN:

152262

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

117

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00549

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000258

Hom.:

Bravo

AF:

0.00165

ESP6500AA

AF:

0.00499

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000527

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.65

DANN

Benign

0.80

DEOGEN2

Benign

0.14

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.33

M_CAP

Benign

0.027

MetaRNN

Benign

0.0067

MetaSVM

Benign

-0.99

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.3

REVEL

Benign

0.095

Sift

Benign

0.37

Sift4G

Benign

0.16

Polyphen

0.47

Vest4

0.052

MVP

0.41

MPC

0.53

ClinPred

0.022

GERP RS

2.1

Varity_R

0.044

gMVP

0.30

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over