10-103449616-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_015916.5(CALHM2):c.326G>A(p.Arg109His) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R109C) has been classified as Uncertain significance.
Frequency
Consequence
NM_015916.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CALHM2 | NM_015916.5 | c.326G>A | p.Arg109His | missense_variant | 3/4 | ENST00000260743.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CALHM2 | ENST00000260743.10 | c.326G>A | p.Arg109His | missense_variant | 3/4 | 1 | NM_015916.5 | P1 | |
CALHM2 | ENST00000369788.7 | c.326G>A | p.Arg109His | missense_variant | 3/4 | 2 | P1 | ||
CALHM2 | ENST00000494180.1 | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251334Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135886
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461566Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727104
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 29, 2021 | The c.326G>A (p.R109H) alteration is located in exon 3 (coding exon 1) of the CALHM2 gene. This alteration results from a G to A substitution at nucleotide position 326, causing the arginine (R) at amino acid position 109 to be replaced by a histidine (H). 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