7-116505995-C-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The NM_198212.3(CAV2):ā€‹c.175C>Gā€‹(p.Leu59Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,612,998 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.000035 ( 2 hom. )

Consequence

CAV2
NM_198212.3 missense

Scores

5
10

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.832
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.28880283).
BP6
Variant 7-116505995-C-G is Benign according to our data. Variant chr7-116505995-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3485518.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CAV2NM_001233.5 linkc.363C>G p.Thr121Thr synonymous_variant Exon 3 of 3 ENST00000222693.5 NP_001224.1 P51636-1Q53X57
CAV2NM_198212.3 linkc.175C>G p.Leu59Val missense_variant Exon 2 of 2 NP_937855.1 P51636-3
CAV2NM_001206747.2 linkc.324C>G p.Thr108Thr synonymous_variant Exon 3 of 3 NP_001193676.1 P51636-2
CAV2NM_001206748.2 linkc.114C>G p.Thr38Thr synonymous_variant Exon 2 of 2 NP_001193677.1 P51636

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CAV2ENST00000222693.5 linkc.363C>G p.Thr121Thr synonymous_variant Exon 3 of 3 1 NM_001233.5 ENSP00000222693.4 P51636-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152158
Hom.:
0
Cov.:
33
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:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000638
AC:
16
AN:
250636
Hom.:
0
AF XY:
0.0000886
AC XY:
12
AN XY:
135408
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:
0.000460
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000349
AC:
51
AN:
1460840
Hom.:
2
Cov.:
30
AF XY:
0.0000468
AC XY:
34
AN XY:
726700
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:
0.000546
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152158
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74336
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:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000130
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Oct 07, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.072
T
BayesDel_noAF
Uncertain
-0.010
CADD
Benign
12
DANN
Uncertain
0.99
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.43
T
M_CAP
Benign
0.0072
T
MetaRNN
Benign
0.29
T
MetaSVM
Benign
-0.62
T
PROVEAN
Benign
0.92
N
REVEL
Benign
0.18
Sift
Benign
0.48
T
Sift4G
Benign
0.58
T
Polyphen
0.99
D
Vest4
0.43
MutPred
0.65
Loss of helix (P = 0.0017);
MVP
0.73
ClinPred
0.11
T
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs759051961; hg19: chr7-116146049; API