2-240587011-C-G
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The ENST00000391984.7(CAPN10):āc.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
ENST00000391984.7 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 2.15
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]
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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 |
---|---|---|---|---|---|---|---|---|
CAPN10 | NM_023083.4 | c.100C>G | p.Leu34Val | missense_variant | 1/12 | ENST00000391984.7 | NP_075571.2 | |
CAPN10 | NM_023085.4 | c.100C>G | p.Leu34Val | missense_variant | 1/10 | NP_075573.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CAPN10 | ENST00000391984.7 | c.100C>G | p.Leu34Val | missense_variant | 1/12 | 1 | NM_023083.4 | ENSP00000375844 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00801 AC: 1219AN: 152254Hom.: 15 Cov.: 33
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GnomAD3 exomes AF: 0.00807 AC: 730AN: 90404Hom.: 5 AF XY: 0.00739 AC XY: 376AN XY: 50886
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GnomAD4 exome AF: 0.00800 AC: 10593AN: 1323390Hom.: 56 Cov.: 31 AF XY: 0.00777 AC XY: 5070AN XY: 652202
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GnomAD4 genome AF: 0.00799 AC: 1217AN: 152368Hom.: 15 Cov.: 33 AF XY: 0.00886 AC XY: 660AN XY: 74520
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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 submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;L;L
MutationTaster
Benign
D;D;D;D;D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
P;.;P;D;D
Vest4
MVP
MPC
ClinPred
T
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at