7-116506084-G-T

Variant names:

• chr7-116506084-G-T
• rs1171200240
• NM_001233.5:c.452G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001233.5(CAV2):​c.452G>T​(p.Cys151Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CAV2 NM_001233.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAV2	NM_001233.5	c.452G>T	p.Cys151Phe	missense_variant	Exon 3 of 3	ENST00000222693.5	NP_001224.1
CAV2	NM_001206747.2	c.413G>T	p.Cys138Phe	missense_variant	Exon 3 of 3		NP_001193676.1
CAV2	NM_198212.3	c.264G>T	p.Met88Ile	missense_variant	Exon 2 of 2		NP_937855.1
CAV2	NM_001206748.2	c.203G>T	p.Cys68Phe	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.452G>T	p.Cys151Phe	missense_variant	Exon 3 of 3	1	NM_001233.5	ENSP00000222693.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461806 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727212

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000434 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Pathogenic	0.91	D
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0047	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.81	T
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.22	T
Polyphen		0.28	B
Vest4		0.27
MutPred		0.38		Gain of disorder (P = 0.1176);
MVP		0.78
MPC		0.81
ClinPred		0.65	D
GERP RS		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.65

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: rs1171200240; hg19: chr7-116146138; COSMIC: COSV56063946; COSMIC: COSV56063946;