7-116506010-G-A

Position:

• chr7-116506010-G-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The ENST00000343213.2(CAV2):​c.190G>A​(p.Ala64Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CAV2 ENST00000343213.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.42

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2748878).
• BP6: Variant 7-116506010-G-A is Benign according to our data. Variant chr7-116506010-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2610157.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAV2	NM_001233.5	c.378G>A	p.Leu126=	synonymous_variant	3/3	ENST00000222693.5	NP_001224.1
CAV2	NM_198212.3	c.190G>A	p.Ala64Thr	missense_variant	2/2		NP_937855.1
CAV2	NM_001206747.2	c.339G>A	p.Leu113=	synonymous_variant	3/3		NP_001193676.1
CAV2	NM_001206748.2	c.129G>A	p.Leu43=	synonymous_variant	2/2		NP_001193677.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAV2	ENST00000222693.5	c.378G>A	p.Leu126=	synonymous_variant	3/3	1	NM_001233.5	ENSP00000222693	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	7.8
DANN	Pathogenic	1.0
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.70	T
MutationTaster	Benign	1.0	D;N
PROVEAN	Benign	1.7	N
REVEL	Benign	0.20
Sift	Uncertain	0.017	D
Sift4G	Benign	0.33	T
Polyphen		0.98	D
Vest4		0.13
MutPred		0.60		Loss of catalytic residue at A64 (P = 0.0155);
MVP		0.79
ClinPred		0.38	T
GERP RS		4.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1793227161; hg19: chr7-116146064;