1-223750973-C-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_001748.5(CAPN2):c.897C>A(p.Asp299Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000572 in 1,399,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001748.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAPN2 | NM_001748.5 | c.897C>A | p.Asp299Glu | missense_variant, splice_region_variant | 7/21 | ENST00000295006.6 | |
CAPN2 | NM_001146068.2 | c.663C>A | p.Asp221Glu | missense_variant, splice_region_variant | 7/21 | ||
CAPN2 | XM_047431344.1 | c.897C>A | p.Asp299Glu | missense_variant, splice_region_variant | 7/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAPN2 | ENST00000295006.6 | c.897C>A | p.Asp299Glu | missense_variant, splice_region_variant | 7/21 | 1 | NM_001748.5 | P1 | |
CAPN2 | ENST00000433674.6 | c.663C>A | p.Asp221Glu | missense_variant, splice_region_variant | 7/21 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000638 AC: 1AN: 156712Hom.: 0 AF XY: 0.0000121 AC XY: 1AN XY: 82452
GnomAD4 exome AF: 0.00000572 AC: 8AN: 1399546Hom.: 0 Cov.: 31 AF XY: 0.00000724 AC XY: 5AN XY: 690326
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 21, 2022 | The c.897C>A (p.D299E) alteration is located in exon 7 (coding exon 7) of the CAPN2 gene. This alteration results from a C to A substitution at nucleotide position 897, causing the aspartic acid (D) at amino acid position 299 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at