2-191835949-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004657.6(CAVIN2):​c.1252G>A​(p.Val418Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000651 in 1,612,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

CAVIN2
NM_004657.6 missense

Scores

6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.87
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36127734).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CAVIN2NM_004657.6 linkuse as main transcriptc.1252G>A p.Val418Met missense_variant 2/2 ENST00000304141.5 NP_004648.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CAVIN2ENST00000304141.5 linkuse as main transcriptc.1252G>A p.Val418Met missense_variant 2/21 NM_004657.6 ENSP00000305675 P1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152222
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000360
AC:
9
AN:
249710
Hom.:
0
AF XY:
0.0000444
AC XY:
6
AN XY:
135110
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000798
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000691
AC:
101
AN:
1460756
Hom.:
0
Cov.:
30
AF XY:
0.0000605
AC XY:
44
AN XY:
726696
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000863
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152222
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000574
Hom.:
0
Bravo
AF:
0.0000151
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 09, 2024The c.1252G>A (p.V418M) alteration is located in exon 2 (coding exon 2) of the SDPR gene. This alteration results from a G to A substitution at nucleotide position 1252, causing the valine (V) at amino acid position 418 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.083
T
BayesDel_noAF
Benign
-0.17
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
T
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.70
T
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.36
T
MetaSVM
Uncertain
0.16
D
MutationTaster
Benign
0.65
D
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-0.79
N
REVEL
Benign
0.23
Sift
Uncertain
0.0010
D
Sift4G
Benign
0.078
T
Polyphen
1.0
D
Vest4
0.17
MutPred
0.29
Gain of catalytic residue at V414 (P = 0.0236);
MVP
0.59
MPC
0.48
ClinPred
0.37
T
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.19
gMVP
0.29

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.

Other links and lift over

dbSNP: rs768293117; hg19: chr2-192700675; COSMIC: COSV58424299; API