chr1-223745433-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001748.5(CAPN2):c.554A>G(p.Tyr185Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001748.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAPN2 | NM_001748.5 | c.554A>G | p.Tyr185Cys | missense_variant | 4/21 | ENST00000295006.6 | |
CAPN2 | NM_001146068.2 | c.320A>G | p.Tyr107Cys | missense_variant | 4/21 | ||
CAPN2 | XM_047431344.1 | c.554A>G | p.Tyr185Cys | missense_variant | 4/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAPN2 | ENST00000295006.6 | c.554A>G | p.Tyr185Cys | missense_variant | 4/21 | 1 | NM_001748.5 | P1 | |
CAPN2 | ENST00000433674.6 | c.320A>G | p.Tyr107Cys | missense_variant | 4/21 | 2 | |||
CAPN2 | ENST00000434648.5 | c.320A>G | p.Tyr107Cys | missense_variant | 4/5 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251386Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135876
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461868Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727240
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 13, 2023 | The c.554A>G (p.Y185C) alteration is located in exon 4 (coding exon 4) of the CAPN2 gene. This alteration results from a A to G substitution at nucleotide position 554, causing the tyrosine (Y) at amino acid position 185 to be replaced by a cysteine (C). 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