rs558378225

Variant names:

• chr12-75282305-T-C
• rs558378225
• NM_001355024.4:c.1444A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001355024.4(CAPS2):​c.1444A>G​(p.Ile482Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,608,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: CAPS2 NM_001355024.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0980
• Publications: 0 publications found

Genes affected

CAPS2 (HGNC:16471): (calcyphosine 2) Calcyphosine-2 is a calcium-binding protein with 2 EF-hand motifs (Wang et al., 2002 [PubMed 11846421]).[supplied by OMIM, Mar 2008]

CAPS2-AS1 (HGNC:40769): (CAPS2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.024314165).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001355024.4. 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
	CAPS2	NM_001355024.4	MANE Select	c.1444A>G	p.Ile482Val	missense	Exon 16 of 17	NP_001341953.2	Q9BXY5-4
	CAPS2	NM_001355023.4		c.1462A>G	p.Ile488Val	missense	Exon 17 of 18	NP_001341952.2
	CAPS2	NM_032606.5		c.1615A>G	p.Ile539Val	missense	Exon 17 of 18	NP_115995.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPS2	ENST00000699294.1	MANE Select	c.1444A>G	p.Ile482Val	missense	Exon 16 of 17	ENSP00000514274.1	Q9BXY5-4
	CAPS2	ENST00000393284.8	TSL:1	c.1558A>G	p.Ile520Val	missense	Exon 16 of 17	ENSP00000376963.4	Q9BXY5-5
	CAPS2	ENST00000409799.6	TSL:1	c.1348A>G	p.Ile450Val	missense	Exon 15 of 16	ENSP00000386977.2	B9A061

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000677 AC: 17 AN: 251192 AF XY: 0.0000810

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000220 AC: 32 AN: 1455912 Hom.: 0 Cov.: 27 AF XY: 0.0000331 AC XY: 24 AN XY: 724806

African (AFR) AF: 0.00 AC: 0 AN: 33346

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.000313 AC: 27 AN: 86146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1106636

Other (OTH) AF: 0.0000166 AC: 1 AN: 60200

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74488

African (AFR) AF: 0.00 AC: 0 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000115 AC: 14

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.069
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.20
DANN	Benign	0.67
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.53	N
PhyloP100		0.098
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.050
Sift	Benign	0.61	T
Sift4G	Benign	0.42	T
Polyphen		0.0020	B
Vest4		0.13
MutPred		0.66		Gain of MoRF binding (P = 0.0882)
MVP		0.27
MPC		0.060
ClinPred		0.025	T
GERP RS		-5.5
Varity_R		0.029
gMVP		0.24
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs558378225; hg19: chr12-75676085;