chr2-240598657-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_023083.4(CAPN10):c.1996A>G(p.Ile666Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.973 in 1,579,140 control chromosomes in the GnomAD database, including 747,191 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. I666F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.98 ( 73164 hom., cov: 33)

Exomes 𝑓: 0.97 ( 674027 hom. )

Consequence

CAPN10
NM_023083.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.09

Publications

35 publications found

Variant links:

Genes affected

CAPN10 (HGNC:1477): (calpain 10) Calpains represent a ubiquitous, well-conserved family of calcium-dependent cysteine proteases. The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large catalytic subunit has four domains: domain I, the N-terminal regulatory domain that is processed upon calpain activation; domain II, the protease domain; domain III, a linker domain of unknown function; and domain IV, the calmodulin-like calcium-binding domain. This gene encodes a large subunit. It is an atypical calpain in that it lacks the calmodulin-like calcium-binding domain and instead has a divergent C-terminal domain. It is similar in organization to calpains 5 and 6. This gene is associated with type 2 or non-insulin-dependent diabetes mellitus (NIDDM), and is located within the NIDDM1 region. Multiple alternative transcript variants have been described for this gene. [provided by RefSeq, Sep 2010]

CAPN10 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: G2P

CAPN10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.433308E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023083.4. 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
	CAPN10	NM_023083.4	MANE Select	c.1996A>G	p.Ile666Val	missense	Exon 12 of 12	NP_075571.2	Q9HC96-1
	CAPN10	NM_023085.4		c.1531A>G	p.Ile511Val	missense	Exon 10 of 10	NP_075573.3	Q9HC96-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CAPN10	ENST00000391984.7	TSL:1 MANE Select	c.1996A>G	p.Ile666Val	missense	Exon 12 of 12	ENSP00000375844.2	Q9HC96-1
CAPN10	ENST00000354082.8	TSL:1	c.1531A>G	p.Ile511Val	missense	Exon 10 of 10	ENSP00000270362.6	Q9HC96-3
CAPN10	ENST00000352879.8	TSL:1	c.394A>G	p.Ile132Val	missense	Exon 4 of 4	ENSP00000289381.6	Q9HC96-8

Frequencies

GnomAD3 genomes

AF:

0.980

AC:

149139

AN:

152180

Hom.:

73102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.994

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.976

Gnomad ASJ

AF:

0.958

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.986

Gnomad FIN

AF:

0.993

Gnomad MID

AF:

0.968

Gnomad NFE

AF:

0.969

Gnomad OTH

AF:

0.974

GnomAD2 exomes

AF:

0.979

AC:

189056

AN:

193162

AF XY:

0.978

show subpopulations

Gnomad AFR exome

AF:

0.996

Gnomad AMR exome

AF:

0.981

Gnomad ASJ exome

AF:

0.956

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.995

Gnomad NFE exome

AF:

0.969

Gnomad OTH exome

AF:

0.975

GnomAD4 exome

AF:

0.972

AC:

1386816

AN:

1426842

Hom.:

674027

Cov.:

AF XY:

0.972

AC XY:

686170

AN XY:

706050

show subpopulations

African (AFR)

AF:

0.995

AC:

33040

AN:

33192

American (AMR)

AF:

0.981

AC:

37215

AN:

37944

Ashkenazi Jewish (ASJ)

AF:

0.955

AC:

24292

AN:

25432

East Asian (EAS)

AF:

1.00

AC:

38542

AN:

38546

South Asian (SAS)

AF:

0.985

AC:

80058

AN:

81300

European-Finnish (FIN)

AF:

0.993

AC:

50048

AN:

50424

Middle Eastern (MID)

AF:

0.965

AC:

5517

AN:

5720

European-Non Finnish (NFE)

AF:

0.968

AC:

1060425

AN:

1095098

Other (OTH)

AF:

0.975

AC:

57679

AN:

59186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

1973

3945

5918

7890

9863

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21458

42916

64374

85832

107290

<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:

0.980

AC:

149260

AN:

152298

Hom.:

73164

Cov.:

AF XY:

0.981

AC XY:

73076

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.994

AC:

41332

AN:

41566

American (AMR)

AF:

0.976

AC:

14931

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.958

AC:

3326

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5166

AN:

5166

South Asian (SAS)

AF:

0.986

AC:

4763

AN:

4830

European-Finnish (FIN)

AF:

0.993

AC:

10557

AN:

10628

Middle Eastern (MID)

AF:

0.973

AC:

286

AN:

294

European-Non Finnish (NFE)

AF:

0.969

AC:

65925

AN:

68010

Other (OTH)

AF:

0.974

AC:

2062

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

149

298

446

595

744

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

916

1832

2748

3664

4580

<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:

0.969

Hom.:

147791

Bravo

AF:

0.979

TwinsUK

AF:

0.971

AC:

3600

ALSPAC

AF:

0.968

AC:

3732

ESP6500AA

AF:

0.995

AC:

4352

ESP6500EA

AF:

0.971

AC:

8312

ExAC

AF:

0.974

AC:

112490

Asia WGS

AF:

0.994

AC:

3456

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.057

(source)

DANN

Benign

0.24

DEOGEN2

Benign

0.095

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.071

MetaRNN

Benign

8.4e-7

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.76

PhyloP100

-2.1

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.25

REVEL

Benign

0.078

Sift

Benign

0.68

Sift4G

Benign

0.29

Polyphen

0.0

Vest4

0.019

MPC

0.29

ClinPred

0.00092

GERP RS

-6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.014

gMVP

0.25

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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