7-116505987-G-A

Position:

• chr7-116505987-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001233.5(CAV2):​c.355G>A​(p.Val119Ile) 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. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CAV2 NM_001233.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.35

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15571684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAV2	NM_001233.5	c.355G>A	p.Val119Ile	missense_variant	3/3	ENST00000222693.5	NP_001224.1
CAV2	NM_001206747.2	c.316G>A	p.Val106Ile	missense_variant	3/3		NP_001193676.1
CAV2	NM_198212.3	c.167G>A	p.Cys56Tyr	missense_variant	2/2		NP_937855.1
CAV2	NM_001206748.2	c.106G>A	p.Val36Ile	missense_variant	2/2		NP_001193677.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAV2	ENST00000222693.5	c.355G>A	p.Val119Ile	missense_variant	3/3	1	NM_001233.5	ENSP00000222693	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.355G>A (p.V119I) alteration is located in exon 3 (coding exon 3) of the CAV2 gene. This alteration results from a G to A substitution at nucleotide position 355, causing the valine (V) at amino acid position 119 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	18
DANN	Benign	0.78
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.046
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.36	T
MutationTaster	Benign	1.0	D;N
PROVEAN	Benign	0.70	N
REVEL	Benign	0.084
Sift	Benign	0.037	D
Sift4G	Benign	0.29	T
Polyphen		0.023	B
Vest4		0.19
MutPred		0.39		Loss of helix (P = 0.0041);
MVP		0.67
ClinPred		0.98	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-116146041;