7-116500470-G-T

Variant names:

• chr7-116500470-G-T
• rs2270188
• NM_001233.5:c.338+23G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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]

CAV2 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CAV2	NM_001233.5	c.338+23G>T		intron_variant	Intron 2 of 2	ENST00000222693.5	NP_001224.1
CAV2	NM_001206747.2	c.299+23G>T		intron_variant	Intron 2 of 2		NP_001193676.1
CAV2	NM_198212.3	c.150+539G>T		intron_variant	Intron 1 of 1		NP_937855.1
CAV2	NM_001206748.2	c.89+23G>T		intron_variant	Intron 1 of 1		NP_001193677.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAV2	ENST00000222693.5	c.338+23G>T		intron_variant	Intron 2 of 2	1	NM_001233.5	ENSP00000222693.4

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

GnomAD2 exomes AF: 0.541 AC: 130712 AN: 241486 AF XY: 0.539

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 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

African (AFR) AF: 0.385 AC: 12797 AN: 33266

American (AMR) AF: 0.612 AC: 27051 AN: 44166

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 12032 AN: 25254

East Asian (EAS) AF: 0.759 AC: 30001 AN: 39530

South Asian (SAS) AF: 0.536 AC: 45173 AN: 84298

European-Finnish (FIN) AF: 0.555 AC: 29329 AN: 52810

Middle Eastern (MID) AF: 0.508 AC: 2595 AN: 5110

European-Non Finnish (NFE) AF: 0.496 AC: 547764 AN: 1104274

Other (OTH) AF: 0.518 AC: 31002 AN: 59814

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

African (AFR) AF: 0.388 AC: 16089 AN: 41422

American (AMR) AF: 0.561 AC: 8570 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1686 AN: 3470

East Asian (EAS) AF: 0.773 AC: 3990 AN: 5162

South Asian (SAS) AF: 0.548 AC: 2640 AN: 4818

European-Finnish (FIN) AF: 0.568 AC: 5979 AN: 10530

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34040 AN: 67968

Other (OTH) AF: 0.501 AC: 1056 AN: 2108

Alfa AF: 0.465 Hom.: 5431

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
PhyloP100		-0.53
Mutation Taster		=100/0	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

Other links and lift over

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