2-240587011-C-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000391984.7(CAPN10):ā€‹c.100C>Gā€‹(p.Leu34Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.008 in 1,475,758 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0080 ( 15 hom., cov: 33)
Exomes š‘“: 0.0080 ( 56 hom. )

Consequence

CAPN10
ENST00000391984.7 missense

Scores

4
14

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.15
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0049797).
BP6
Variant 2-240587011-C-G is Benign according to our data. Variant chr2-240587011-C-G is described in ClinVar as [Benign]. Clinvar id is 716765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-240587011-C-G is described in Lovd as [Likely_benign].
BS2
High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CAPN10NM_023083.4 linkuse as main transcriptc.100C>G p.Leu34Val missense_variant 1/12 ENST00000391984.7 NP_075571.2
CAPN10NM_023085.4 linkuse as main transcriptc.100C>G p.Leu34Val missense_variant 1/10 NP_075573.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CAPN10ENST00000391984.7 linkuse as main transcriptc.100C>G p.Leu34Val missense_variant 1/121 NM_023083.4 ENSP00000375844 P1Q9HC96-1

Frequencies

GnomAD3 genomes
AF:
0.00801
AC:
1219
AN:
152254
Hom.:
15
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00169
Gnomad AMI
AF:
0.00768
Gnomad AMR
AF:
0.00373
Gnomad ASJ
AF:
0.00634
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000413
Gnomad FIN
AF:
0.0292
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0108
Gnomad OTH
AF:
0.00764
GnomAD3 exomes
AF:
0.00807
AC:
730
AN:
90404
Hom.:
5
AF XY:
0.00739
AC XY:
376
AN XY:
50886
show subpopulations
Gnomad AFR exome
AF:
0.00151
Gnomad AMR exome
AF:
0.00329
Gnomad ASJ exome
AF:
0.00757
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000237
Gnomad FIN exome
AF:
0.0209
Gnomad NFE exome
AF:
0.0108
Gnomad OTH exome
AF:
0.00508
GnomAD4 exome
AF:
0.00800
AC:
10593
AN:
1323390
Hom.:
56
Cov.:
31
AF XY:
0.00777
AC XY:
5070
AN XY:
652202
show subpopulations
Gnomad4 AFR exome
AF:
0.00115
Gnomad4 AMR exome
AF:
0.00362
Gnomad4 ASJ exome
AF:
0.00748
Gnomad4 EAS exome
AF:
0.0000354
Gnomad4 SAS exome
AF:
0.000251
Gnomad4 FIN exome
AF:
0.0226
Gnomad4 NFE exome
AF:
0.00857
Gnomad4 OTH exome
AF:
0.00575
GnomAD4 genome
AF:
0.00799
AC:
1217
AN:
152368
Hom.:
15
Cov.:
33
AF XY:
0.00886
AC XY:
660
AN XY:
74520
show subpopulations
Gnomad4 AFR
AF:
0.00168
Gnomad4 AMR
AF:
0.00372
Gnomad4 ASJ
AF:
0.00634
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.0292
Gnomad4 NFE
AF:
0.0108
Gnomad4 OTH
AF:
0.00709
Alfa
AF:
0.00940
Hom.:
3
Bravo
AF:
0.00562
TwinsUK
AF:
0.00728
AC:
27
ALSPAC
AF:
0.00856
AC:
33
ESP6500AA
AF:
0.000982
AC:
4
ESP6500EA
AF:
0.00568
AC:
46
ExAC
AF:
0.00293
AC:
300
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.43
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.17
T;.;.;.;.
Eigen
Benign
0.081
Eigen_PC
Benign
0.029
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Uncertain
0.88
D;D;D;D;D
MetaRNN
Benign
0.0050
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
L;.;L;L;L
MutationTaster
Benign
0.99
D;D;D;D;D;N
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-0.96
N;N;N;N;N
REVEL
Benign
0.11
Sift
Benign
0.096
T;T;T;T;T
Sift4G
Benign
0.11
T;T;T;T;T
Polyphen
0.95
P;.;P;D;D
Vest4
0.15
MVP
0.66
MPC
0.56
ClinPred
0.018
T
GERP RS
2.5
Varity_R
0.10
gMVP
0.26

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs138005500; hg19: chr2-241526428; COSMIC: COSV54376248; COSMIC: COSV54376248; API