rs17138765

Variant names:

• chr7-116497472-G-A
• rs17138765
• ENST00000462876.5:n.1007-297G>A

Variant summary

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

The ENST00000462876.5(CAV2):​n.1007-297G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,212 control chromosomes in the GnomAD database, including 973 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 0.10 (973 hom., cov: 32)
• Consequence: CAV2 ENST00000462876.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• Publications: 6 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

CAV2-DT (HGNC:40129):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000462876.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAV2-DT	NR_188009.1		n.163+1882C>T		intron	N/A
	CAV2-DT	NR_188010.1		n.163+1882C>T		intron	N/A
	CAV2-DT	NR_188011.1		n.163+1882C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAV2	ENST00000462876.5	TSL:1	n.1007-297G>A		intron	N/A
	CAV2	ENST00000467035.5	TSL:1	n.753-297G>A		intron	N/A
	CAV2	ENST00000472470.5	TSL:1	n.407-297G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15519 AN: 152096 Hom.: 967 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0701

Gnomad ASJ AF: 0.0899

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0216

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0846

Gnomad OTH AF: 0.105

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.102 AC: 15547 AN: 152212 Hom.: 973 Cov.: 32 AF XY: 0.0980 AC XY: 7295 AN XY: 74414

African (AFR) AF: 0.175 AC: 7265 AN: 41524

American (AMR) AF: 0.0699 AC: 1069 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0899 AC: 312 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0212 AC: 102 AN: 4818

European-Finnish (FIN) AF: 0.0651 AC: 690 AN: 10598

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0845 AC: 5749 AN: 68012

Other (OTH) AF: 0.103 AC: 219 AN: 2116

Alfa AF: 0.0917 Hom.: 138

Bravo AF: 0.108

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.47
PhyloP100		-0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17138765; hg19: chr7-116137526;