2-191846883-C-T

Variant names:

• chr2-191846883-C-T
• rs920625240
• NM_004657.6:c.43G>A

Variant summary

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

The NM_004657.6(CAVIN2):​c.43G>A​(p.Gly15Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CAVIN2 NM_004657.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.132

Genes affected

CAVIN2 (HGNC:10690): (caveolae associated protein 2) This gene encodes a calcium-independent phospholipid-binding protein whose expression increases in serum-starved cells. This protein is a substrate for protein kinase C (PKC) phosphorylation and recruits polymerase I and transcript release factor (PTRF) to caveolae. Removal of this protein causes caveolae loss and its over-expression results in caveolae deformation and membrane tubulation.[provided by RefSeq, Sep 2009]

CAVIN2-AS1 (HGNC:40517): (CAVIN2 and TMEFF2 antisense RNA 1)

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=0.14181632).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAVIN2	NM_004657.6	c.43G>A	p.Gly15Arg	missense_variant	Exon 1 of 2	ENST00000304141.5	NP_004648.1
CAVIN2-AS1	NR_187184.1	n.284+112C>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAVIN2	ENST00000304141.5	c.43G>A	p.Gly15Arg	missense_variant	Exon 1 of 2	1	NM_004657.6	ENSP00000305675.4
CAVIN2-AS1	ENST00000424116.7	n.238+112C>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461474 Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4 AN XY: 727050

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.00000756

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.43G>A (p.G15R) alteration is located in exon 1 (coding exon 1) of the SDPR gene. This alteration results from a G to A substitution at nucleotide position 43, causing the glycine (G) at amino acid position 15 to be replaced by an arginine (R). 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	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.82
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.93	T
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.080
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.41	T
Polyphen		0.74	P
Vest4		0.13
MutPred		0.18		Loss of loop (P = 2e-04);
MVP		0.46
MPC		0.47
ClinPred		0.16	T
GERP RS		3.9
Varity_R		0.099
gMVP		0.22

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

LitVar

Other links and lift over

dbSNP: rs920625240; hg19: chr2-192711609;