7-116500470-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001233.5(CAV2):c.338+23G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 1,600,476 control chromosomes in the GnomAD database, including 209,530 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.

• Frequency:
  • Genomes: 𝑓 0.49 (18909 hom., cov: 32)
  • Exomes 𝑓: 0.51 (190621 hom.)
• Consequence: CAV2 NM_001233.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAV2	NM_001233.5	c.338+23G>T		intron_variant		ENST00000222693.5
CAV2	NM_001206747.2	c.299+23G>T		intron_variant
CAV2	NM_001206748.2	c.89+23G>T		intron_variant
CAV2	NM_198212.3	c.150+539G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAV2	ENST00000222693.5	c.338+23G>T		intron_variant		1	NM_001233.5	P1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74505 AN: 151836 Hom.: 18887 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.496

GnomAD3 exomes AF: 0.541 AC: 130712 AN: 241486 Hom.: 36322 AF XY: 0.539 AC XY: 70241 AN XY: 130334

Gnomad AFR exome AF: 0.389

Gnomad AMR exome AF: 0.620

Gnomad ASJ exome AF: 0.482

Gnomad EAS exome AF: 0.786

Gnomad SAS exome AF: 0.547

Gnomad FIN exome AF: 0.558

Gnomad NFE exome AF: 0.499

Gnomad OTH exome AF: 0.523

GnomAD4 exome AF: 0.509 AC: 737744 AN: 1448522 Hom.: 190621 Cov.: 33 AF XY: 0.510 AC XY: 366887 AN XY: 719596

Gnomad4 AFR exome AF: 0.385

Gnomad4 AMR exome AF: 0.612

Gnomad4 ASJ exome AF: 0.476

Gnomad4 EAS exome AF: 0.759

Gnomad4 SAS exome AF: 0.536

Gnomad4 FIN exome AF: 0.555

Gnomad4 NFE exome AF: 0.496

Gnomad4 OTH exome AF: 0.518

GnomAD4 genome AF: 0.491 AC: 74568 AN: 151954 Hom.: 18909 Cov.: 32 AF XY: 0.499 AC XY: 37048 AN XY: 74234

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.501

Alfa AF: 0.493 Hom.: 4239

Bravo AF: 0.483

Asia WGS AF: 0.680 AC: 2360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	7.9
Dann	Benign	0.87

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: rs2270188; hg19: chr7-116140524; COSMIC: COSV56064253; COSMIC: COSV56064253;