rs8940

Variant names:

• chr7-116506020-C-G
• rs8940
• NM_001233.5:c.388C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001233.5(CAV2):​c.388C>G​(p.Gln130Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,612,374 control chromosomes in the GnomAD database, including 24,883 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.17 (2305 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22578 hom.)
• Consequence: CAV2 NM_001233.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.47

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014756322).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAV2	NM_001233.5	c.388C>G	p.Gln130Glu	missense_variant	Exon 3 of 3	ENST00000222693.5	NP_001224.1
CAV2	NM_001206747.2	c.349C>G	p.Gln117Glu	missense_variant	Exon 3 of 3		NP_001193676.1
CAV2	NM_198212.3	c.200C>G	p.Ala67Gly	missense_variant	Exon 2 of 2		NP_937855.1
CAV2	NM_001206748.2	c.139C>G	p.Gln47Glu	missense_variant	Exon 2 of 2		NP_001193677.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAV2	ENST00000222693.5	c.388C>G	p.Gln130Glu	missense_variant	Exon 3 of 3	1	NM_001233.5	ENSP00000222693.4

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25333 AN: 152036 Hom.: 2308 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.0690

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.182

GnomAD2 exomes AF: 0.151 AC: 37877 AN: 251226 AF XY: 0.157

Gnomad AFR exome AF: 0.187

Gnomad AMR exome AF: 0.106

Gnomad ASJ exome AF: 0.268

Gnomad EAS exome AF: 0.00772

Gnomad FIN exome AF: 0.0721

Gnomad NFE exome AF: 0.178

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.170 AC: 247598 AN: 1460220 Hom.: 22578 Cov.: 31 AF XY: 0.171 AC XY: 124405 AN XY: 726504

Gnomad4 AFR exome AF: 0.183 AC: 6122 AN: 33452

Gnomad4 AMR exome AF: 0.111 AC: 4942 AN: 44718

Gnomad4 ASJ exome AF: 0.270 AC: 7059 AN: 26124

Gnomad4 EAS exome AF: 0.00393 AC: 156 AN: 39692

Gnomad4 SAS exome AF: 0.182 AC: 15707 AN: 86190

Gnomad4 FIN exome AF: 0.0748 AC: 3998 AN: 53414

Gnomad4 NFE exome AF: 0.178 AC: 197934 AN: 1110532

Gnomad4 Remaining exome AF: 0.172 AC: 10348 AN: 60332

GnomAD4 genome AF: 0.167 AC: 25337 AN: 152154 Hom.: 2305 Cov.: 32 AF XY: 0.161 AC XY: 11988 AN XY: 74398

Gnomad4 AFR AF: 0.187 AC: 0.187407 AN: 0.187407

Gnomad4 AMR AF: 0.152 AC: 0.151918 AN: 0.151918

Gnomad4 ASJ AF: 0.261 AC: 0.260519 AN: 0.260519

Gnomad4 EAS AF: 0.0102 AC: 0.0102159 AN: 0.0102159

Gnomad4 SAS AF: 0.179 AC: 0.178928 AN: 0.178928

Gnomad4 FIN AF: 0.0690 AC: 0.0690175 AN: 0.0690175

Gnomad4 NFE AF: 0.177 AC: 0.176805 AN: 0.176805

Gnomad4 OTH AF: 0.179 AC: 0.179317 AN: 0.179317

Alfa AF: 0.188 Hom.: 978

Bravo AF: 0.174

TwinsUK AF: 0.168 AC: 622

ALSPAC AF: 0.182 AC: 702

ESP6500AA AF: 0.192 AC: 845

ESP6500EA AF: 0.194 AC: 1670

ExAC AF: 0.153 AC: 18571

Asia WGS AF: 0.0820 AC: 287 AN: 3478

EpiCase AF: 0.190

EpiControl AF: 0.195

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	23
DANN	Uncertain	0.99
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.98	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.25
Sift	Benign	0.12	T
Sift4G	Benign	0.24	T
Polyphen		1.0	D
Vest4		0.32
ClinPred		0.017	T
GERP RS		5.9
Varity_R		0.52
Mutation Taster		=60/40	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8940; hg19: chr7-116146074; COSMIC: COSV56063971; COSMIC: COSV56063971;