rs745902607
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001006630.2(CHRM2):āc.1189A>Gā(p.Ile397Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000424 in 1,460,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_001006630.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRM2 | NM_001006630.2 | c.1189A>G | p.Ile397Val | missense_variant | 4/4 | ENST00000680005.1 | |
LOC349160 | NR_046103.1 | n.341+16740T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRM2 | ENST00000680005.1 | c.1189A>G | p.Ile397Val | missense_variant | 4/4 | NM_001006630.2 | P1 | ||
ENST00000586239.5 | n.273+16740T>C | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000400 AC: 10AN: 250298Hom.: 0 AF XY: 0.0000739 AC XY: 10AN XY: 135288
GnomAD4 exome AF: 0.0000424 AC: 62AN: 1460718Hom.: 0 Cov.: 31 AF XY: 0.0000509 AC XY: 37AN XY: 726722
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Strand Center for Genomics and Personalized Medicine, Strand Life Sciences Pvt Ltd | - | The novel heterozygous missense variant p.Ile397Val is caused by a substitution within exon 4. The altered amino acid, is a conserved residue within the helical transmembrane domain 6 of CHRM2. Another CHRM2 missense variant, p.Cys176Trp, has been observed in 12 patients from seven unrelated DCM families. The variant was not observed in the additional 139 sporadic DCM patients or the 450 normal volunteers screened. The variant was reported to be associated with an early onset of DCM and was found to segregate in an autosomal dominant manner, with additional phenotypes of sudden death and severe arrhythmia, amongst the affected family members [PMID:18451336]. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at