7-136868746-GCACACACACACACACA-GCACACACACACACACACACACACACA

Variant names:

• chr7-136868746-G-GCACACACACA
• rs35916399
• NM_001006630.2:c.-510_-501dupCACACACACA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001006630.2(CHRM2):​c.-510_-501dupCACACACACA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 0)
• Consequence: CHRM2 NM_001006630.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214
• Publications: 3 publications found

Genes affected

CHRM2 (HGNC:1951): (cholinergic receptor muscarinic 2) The muscarinic cholinergic receptors belong to a larger family of G protein-coupled receptors. The functional diversity of these receptors is defined by the binding of acetylcholine to these receptors and includes cellular responses such as adenylate cyclase inhibition, phosphoinositide degeneration, and potassium channel mediation. Muscarinic receptors influence many effects of acetylcholine in the central and peripheral nervous system. The muscarinic cholinergic receptor 2 is involved in mediation of bradycardia and a decrease in cardiac contractility. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2008]

ENSG00000234352 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006630.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	NM_001006630.2	MANE Select	c.-510_-501dupCACACACACA		5_prime_UTR	Exon 1 of 4	NP_001006631.1	P08172
	CHRM2	NM_001006627.3		c.-432_-423dupCACACACACA		5_prime_UTR	Exon 1 of 3	NP_001006628.1	A4D1Q0
	CHRM2	NM_001378972.1		c.-622_-613dupCACACACACA		5_prime_UTR	Exon 1 of 5	NP_001365901.1	P08172

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	ENST00000680005.1	MANE Select	c.-510_-501dupCACACACACA		5_prime_UTR	Exon 1 of 4	ENSP00000505686.1	P08172
	CHRM2	ENST00000445907.6	TSL:1	c.-432_-423dupCACACACACA		5_prime_UTR	Exon 1 of 3	ENSP00000399745.2	P08172
	ENSG00000234352	ENST00000439694.6	TSL:1	n.656-82865_656-82856dupTGTGTGTGTG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000134 AC: 2 AN: 149280 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000491

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000134 AC: 2 AN: 149280 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 72694

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000491 AC: 2 AN: 40694

American (AMR) AF: 0.00 AC: 0 AN: 15012

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3434

East Asian (EAS) AF: 0.00 AC: 0 AN: 4940

South Asian (SAS) AF: 0.00 AC: 0 AN: 4692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67136

Other (OTH) AF: 0.00 AC: 0 AN: 2054

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000983081), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 771

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.21

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs35916399; hg19: chr7-136553493;