12-75293274-C-T

Variant names:

• chr12-75293274-C-T
• rs375186529
• NM_001355024.4:c.1024G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001355024.4(CAPS2):​c.1024G>A​(p.Asp342Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000811 in 1,602,520 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D342H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: CAPS2 NM_001355024.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.06
• Publications: 2 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1024G>A	p.Asp342Asn	missense	Exon 12 of 17	NP_001341953.2	Q9BXY5-4
	CAPS2	NM_001355023.4		c.1042G>A	p.Asp348Asn	missense	Exon 13 of 18	NP_001341952.2
	CAPS2	NM_032606.5		c.1195G>A	p.Asp399Asn	missense	Exon 13 of 18	NP_115995.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPS2	ENST00000699294.1	MANE Select	c.1024G>A	p.Asp342Asn	missense	Exon 12 of 17	ENSP00000514274.1	Q9BXY5-4
	CAPS2	ENST00000393284.8	TSL:1	c.1138G>A	p.Asp380Asn	missense	Exon 12 of 17	ENSP00000376963.4	Q9BXY5-5
	CAPS2	ENST00000409799.6	TSL:1	c.928G>A	p.Asp310Asn	missense	Exon 11 of 16	ENSP00000386977.2	B9A061

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151680 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249312 AF XY: 0.00

Gnomad AFR exome AF: 0.0000618

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: 0.00

GnomAD4 exome AF: 0.00000758 AC: 11 AN: 1450840 Hom.: 0 Cov.: 29 AF XY: 0.00000692 AC XY: 5 AN XY: 722046

African (AFR) AF: 0.00 AC: 0 AN: 33288

American (AMR) AF: 0.00 AC: 0 AN: 44276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26048

East Asian (EAS) AF: 0.00 AC: 0 AN: 39430

South Asian (SAS) AF: 0.00 AC: 0 AN: 85406

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000997 AC: 11 AN: 1103690

Other (OTH) AF: 0.00 AC: 0 AN: 59984

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151680 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74094

African (AFR) AF: 0.0000483 AC: 2 AN: 41404

American (AMR) AF: 0.00 AC: 0 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67736

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.58
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		4.1
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.48
MVP		0.67
MPC		0.17
ClinPred		0.69	D
GERP RS		3.7
Varity_R		0.47
gMVP		0.47
Mutation Taster		=252/48	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: rs375186529; hg19: chr12-75687054;