NM_001006630.2:c.-124-41363_-124-41358delGTTGTT

Variant names:

• chr7-136950783-CTGTTGT-C
• rs200954535
• NM_001006630.2:c.-124-41363_-124-41358delGTTGTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001006630.2(CHRM2):​c.-124-41363_-124-41358delGTTGTT variant causes a intron 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 0.0024 (2 hom., cov: 16)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 gene

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.-124-41363_-124-41358delGTTGTT		intron	N/A	NP_001006631.1	P08172
	CHRM2	NM_000739.3		c.-124-41363_-124-41358delGTTGTT		intron	N/A	NP_000730.1	P08172
	CHRM2	NM_001006626.3		c.-202-179_-202-174delGTTGTT		intron	N/A	NP_001006627.1	A4D1Q0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	ENST00000680005.1	MANE Select	c.-124-41403_-124-41398delTGTTGT		intron	N/A	ENSP00000505686.1	P08172
	CHRM2	ENST00000320658.9	TSL:1	c.-46-64036_-46-64031delTGTTGT		intron	N/A	ENSP00000319984.5	P08172
	CHRM2	ENST00000401861.1	TSL:1	c.-202-219_-202-214delTGTTGT		intron	N/A	ENSP00000384401.1	P08172

Frequencies

GnomAD3 genomes AF: 0.00243 AC: 364 AN: 149672 Hom.: 2 Cov.: 16

Gnomad AFR AF: 0.00571

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00215

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.000204

Gnomad SAS AF: 0.000654

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00133

Gnomad OTH AF: 0.00194

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00244 AC: 365 AN: 149778 Hom.: 2 Cov.: 16 AF XY: 0.00237 AC XY: 173 AN XY: 72932

African (AFR) AF: 0.00569 AC: 233 AN: 40938

American (AMR) AF: 0.00215 AC: 32 AN: 14904

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3462

East Asian (EAS) AF: 0.000205 AC: 1 AN: 4886

South Asian (SAS) AF: 0.000654 AC: 3 AN: 4586

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00133 AC: 90 AN: 67504

Other (OTH) AF: 0.00240 AC: 5 AN: 2084

Alfa AF: 0.000766 Hom.: 75

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.19

Splicing

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

Other links and lift over

dbSNP: rs200954535; hg19: chr7-136635530;