7-116506008-C-T

Variant names:

• chr7-116506008-C-T
• ENST00000343213.2:c.188C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_198212.3(CAV2):​c.188C>T​(p.Ser63Phe) 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. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CAV2 NM_198212.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.113
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12629563).
• BP6: Variant 7-116506008-C-T is Benign according to our data. Variant chr7-116506008-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3485521.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198212.3. 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	NM_001233.5	MANE Select	c.376C>T	p.Leu126Leu	synonymous	Exon 3 of 3	NP_001224.1	Q53X57
	CAV2	NM_198212.3		c.188C>T	p.Ser63Phe	missense	Exon 2 of 2	NP_937855.1	P51636-3
	CAV2	NM_001206747.2		c.337C>T	p.Leu113Leu	synonymous	Exon 3 of 3	NP_001193676.1	P51636-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAV2	ENST00000343213.2	TSL:1	c.188C>T	p.Ser63Phe	missense	Exon 2 of 2	ENSP00000345679.2	P51636-3
	CAV2	ENST00000222693.5	TSL:1 MANE Select	c.376C>T	p.Leu126Leu	synonymous	Exon 3 of 3	ENSP00000222693.4	P51636-1
	CAV2	ENST00000462876.5	TSL:1	n.1761C>T		non_coding_transcript_exon	Exon 14 of 14

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	10
DANN	Benign	0.93
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.90	T
PhyloP100		0.11
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.029
Sift	Benign	0.067	T
Sift4G	Benign	0.57	T
Polyphen		0.20	B
Vest4		0.14
MutPred		0.42		Gain of sheet (P = 0.0028)
MVP		0.73
ClinPred		0.096	T
GERP RS		0.91
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

hg19: chr7-116146062;