1-223747021-A-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001748.5(CAPN2):c.585A>G(p.Leu195=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,613,796 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 0 hom. )
Consequence
CAPN2
NM_001748.5 synonymous
NM_001748.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.357
Genes affected
CAPN2 (HGNC:1479): (calpain 2) The calpains, calcium-activated neutral proteases, are nonlysosomal, intracellular cysteine proteases. The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. The ubiquitous enzymes consist of heterodimers with distinct large, catalytic subunits associated with a common small, regulatory subunit. This gene encodes the large subunit of the ubiquitous enzyme, calpain 2. Multiple heterogeneous transcriptional start sites in the 5' UTR have been reported. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
?
Variant 1-223747021-A-G is Benign according to our data. Variant chr1-223747021-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2639920.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.357 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAPN2 | NM_001748.5 | c.585A>G | p.Leu195= | synonymous_variant | 5/21 | ENST00000295006.6 | |
CAPN2 | NM_001146068.2 | c.351A>G | p.Leu117= | synonymous_variant | 5/21 | ||
CAPN2 | XM_047431344.1 | c.585A>G | p.Leu195= | synonymous_variant | 5/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAPN2 | ENST00000295006.6 | c.585A>G | p.Leu195= | synonymous_variant | 5/21 | 1 | NM_001748.5 | P1 | |
CAPN2 | ENST00000433674.6 | c.351A>G | p.Leu117= | synonymous_variant | 5/21 | 2 | |||
CAPN2 | ENST00000434648.5 | c.351A>G | p.Leu117= | synonymous_variant | 5/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152166Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251388Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135854
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GnomAD4 exome AF: 0.0000315 AC: 46AN: 1461630Hom.: 0 Cov.: 33 AF XY: 0.0000275 AC XY: 20AN XY: 727144
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74326
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2022 | CAPN2: BP4, BP7 - |
Computational scores
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Name
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Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at