2-191846681-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_004657.6(CAVIN2):​c.245G>C​(p.Arg82Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CAVIN2
NM_004657.6 missense

Scores

7
9
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.08
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-AS1 (HGNC:40517): (CAVIN2 and TMEFF2 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.823

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CAVIN2NM_004657.6 linkc.245G>C p.Arg82Pro missense_variant Exon 1 of 2 ENST00000304141.5 NP_004648.1 O95810
CAVIN2-AS1NR_187184.1 linkn.194C>G non_coding_transcript_exon_variant Exon 1 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CAVIN2ENST00000304141.5 linkc.245G>C p.Arg82Pro missense_variant Exon 1 of 2 1 NM_004657.6 ENSP00000305675.4 O95810
CAVIN2-AS1ENST00000424116.7 linkn.148C>G non_coding_transcript_exon_variant Exon 1 of 3 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251414
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135886
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:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461880
Hom.:
0
Cov.:
34
AF XY:
0.00000413
AC XY:
3
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000247
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 17, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.245G>C (p.R82P) alteration is located in exon 1 (coding exon 1) of the SDPR gene. This alteration results from a G to C substitution at nucleotide position 245, causing the arginine (R) at amino acid position 82 to be replaced by a proline (P). 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
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Pathogenic
0.25
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Benign
0.30
T
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.91
D
M_CAP
Uncertain
0.14
D
MetaRNN
Pathogenic
0.82
D
MetaSVM
Uncertain
0.15
D
PrimateAI
Uncertain
0.59
T
PROVEAN
Pathogenic
-5.3
D
REVEL
Uncertain
0.57
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0080
D
Polyphen
1.0
D
Vest4
0.86
MutPred
0.47
Loss of MoRF binding (P = 0.0748);
MVP
0.79
MPC
1.2
ClinPred
0.92
D
GERP RS
4.6
Varity_R
0.94
gMVP
0.80

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: rs767156465; hg19: chr2-192711407; API