rs375186529

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-75293274-C-G
• chr12-75293274-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001355024.4(CAPS2):​c.1024G>C​(p.Asp342His) variant causes a missense change. The variant allele was found at a frequency of 0.0000132 in 151,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CAPS2 NM_001355024.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.928

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>C	p.Asp342His	missense	Exon 12 of 17	NP_001341953.2	Q9BXY5-4
	CAPS2	NM_001355023.4		c.1042G>C	p.Asp348His	missense	Exon 13 of 18	NP_001341952.2
	CAPS2	NM_032606.5		c.1195G>C	p.Asp399His	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>C	p.Asp342His	missense	Exon 12 of 17	ENSP00000514274.1	Q9BXY5-4
	CAPS2	ENST00000393284.8	TSL:1	c.1138G>C	p.Asp380His	missense	Exon 12 of 17	ENSP00000376963.4	Q9BXY5-5
	CAPS2	ENST00000409799.6	TSL:1	c.928G>C	p.Asp310His	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

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000207 AC: 3 AN: 1450840 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 722046

African (AFR) AF: 0.0000901 AC: 3 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: 0.00 AC: 0 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: 0.0000135 AC XY: 1 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: 0.0000189

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	Uncertain	0.44
BayesDel_addAF	Benign	0.0065	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.13
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Benign	-0.50	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		4.1
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.69		Loss of catalytic residue at D399 (P = 0.1303)
MVP		0.70
MPC		0.44
ClinPred		0.99	D
GERP RS		3.7
Varity_R		0.78
gMVP		0.61

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;