Genetic Variant CAPS2:p.His321Asn (chr12-75293337-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001355024.4(CAPS2):c.961C>A(p.His321Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000627 in 1,611,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

CAPS2
NM_001355024.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.33

Publications

0 publications found

Variant links:

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 links:

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

CAPS2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.109328896).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CAPS2	NM_001355024.4	MANE Select	c.961C>A	p.His321Asn	missense	Exon 12 of 17	NP_001341953.2	Q9BXY5-4
CAPS2	NM_001355023.4		c.979C>A	p.His327Asn	missense	Exon 13 of 18	NP_001341952.2
CAPS2	NM_032606.5		c.1132C>A	p.His378Asn	missense	Exon 13 of 18	NP_115995.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CAPS2	ENST00000699294.1	MANE Select	c.961C>A	p.His321Asn	missense	Exon 12 of 17	ENSP00000514274.1	Q9BXY5-4
CAPS2	ENST00000393284.8	TSL:1	c.1075C>A	p.His359Asn	missense	Exon 12 of 17	ENSP00000376963.4	Q9BXY5-5
CAPS2	ENST00000409799.6	TSL:1	c.865C>A	p.His289Asn	missense	Exon 11 of 16	ENSP00000386977.2	B9A061

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000723

AC:

AN:

248956

AF XY:

0.0000520

show subpopulations

Gnomad AFR exome

AF:

0.000805

Gnomad AMR exome

AF:

0.000119

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:

0.000165

GnomAD4 exome

AF:

0.0000350

AC:

AN:

1459180

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

725946

show subpopulations

African (AFR)

AF:

0.00105

AC:

AN:

33372

American (AMR)

AF:

0.000113

AC:

AN:

44356

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39396

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53254

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1110862

Other (OTH)

AF:

0.000116

AC:

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000329

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.000941

AC:

AN:

41436

American (AMR)

AF:

0.000589

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68000

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000385

Hom.:

Bravo

AF:

0.000351

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.59

M_CAP

Benign

0.0072

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

5.3

PrimateAI

Benign

0.44

PROVEAN

Benign

-2.4

REVEL

Benign

0.16

Sift

Uncertain

0.027

Sift4G

Benign

0.11

Polyphen

0.70

Vest4

0.46

MVP

0.53

MPC

0.080

ClinPred

0.090

GERP RS

4.8

Varity_R

0.16

gMVP

0.47

Mutation Taster

=212/88

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over