rs965790005

Variant names:

• chr12-75293250-T-G
• rs965790005
• NM_001355024.4:c.1048A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001355024.4(CAPS2):​c.1048A>C​(p.Lys350Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000828 in 1,570,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000078 (0 hom.)
• Consequence: CAPS2 NM_001355024.4 missense, splice_region
• Scores: Splicing: ADA: 0.9115
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.28
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26232415).

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.1048A>C	p.Lys350Gln	missense splice_region	Exon 12 of 17	NP_001341953.2	Q9BXY5-4
	CAPS2	NM_001355023.4		c.1066A>C	p.Lys356Gln	missense splice_region	Exon 13 of 18	NP_001341952.2
	CAPS2	NM_032606.5		c.1219A>C	p.Lys407Gln	missense splice_region	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.1048A>C	p.Lys350Gln	missense splice_region	Exon 12 of 17	ENSP00000514274.1	Q9BXY5-4
	CAPS2	ENST00000393284.8	TSL:1	c.1162A>C	p.Lys388Gln	missense splice_region	Exon 12 of 17	ENSP00000376963.4	Q9BXY5-5
	CAPS2	ENST00000409799.6	TSL:1	c.952A>C	p.Lys318Gln	missense splice_region	Exon 11 of 16	ENSP00000386977.2	B9A061

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152178 Hom.: 0 Cov.: 31

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000775 AC: 11 AN: 1418720 Hom.: 0 Cov.: 25 AF XY: 0.00000283 AC XY: 2 AN XY: 707776

African (AFR) AF: 0.00 AC: 0 AN: 32318

American (AMR) AF: 0.00 AC: 0 AN: 42436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25724

East Asian (EAS) AF: 0.00 AC: 0 AN: 39232

South Asian (SAS) AF: 0.00 AC: 0 AN: 82742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52992

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5662

European-Non Finnish (NFE) AF: 0.0000102 AC: 11 AN: 1078610

Other (OTH) AF: 0.00 AC: 0 AN: 59004

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152178 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74342

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15276

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

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	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-0.088
Eigen_PC	Benign	-0.029
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.3
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.060
Sift	Benign	0.069	T
Sift4G	Benign	0.12	T
Polyphen		0.31	B
Vest4		0.44
MutPred		0.41		Loss of ubiquitination at K407 (P = 0.0059)
MVP		0.39
MPC		0.13
ClinPred		0.46	T
GERP RS		4.6
Varity_R		0.21
gMVP		0.41
Mutation Taster		=276/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.91
dbscSNV1_RF	Benign	0.67
SpliceAI score (max)		0.14		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: rs965790005; hg19: chr12-75687030;