NM_001006630.2:c.794C>T

Variant names:

• chr7-137015659-C-T
• rs1554437349
• NM_001006630.2:c.794C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001006630.2(CHRM2):​c.794C>T​(p.Ala265Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: CHRM2 NM_001006630.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 5.16
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12485647).

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.794C>T	p.Ala265Val	missense	Exon 4 of 4	NP_001006631.1	P08172
	CHRM2	NM_000739.3		c.794C>T	p.Ala265Val	missense	Exon 4 of 4	NP_000730.1	P08172
	CHRM2	NM_001006626.3		c.794C>T	p.Ala265Val	missense	Exon 5 of 5	NP_001006627.1	A4D1Q0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	ENST00000680005.1	MANE Select	c.794C>T	p.Ala265Val	missense	Exon 4 of 4	ENSP00000505686.1	P08172
	CHRM2	ENST00000320658.9	TSL:1	c.794C>T	p.Ala265Val	missense	Exon 3 of 3	ENSP00000319984.5	P08172
	CHRM2	ENST00000401861.1	TSL:1	c.794C>T	p.Ala265Val	missense	Exon 5 of 5	ENSP00000384401.1	P08172

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461046 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 726844

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39536

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111602

Other (OTH) AF: 0.0000829 AC: 5 AN: 60340

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Dilated Cardiomyopathy, Dominant (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.091	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.095
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.49	N
PhyloP100		5.2
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.057
Sift	Benign	0.61	T
Sift4G	Benign	0.32	T
Polyphen		0.0010	B
Vest4		0.057
MutPred		0.41		Gain of methylation at K264 (P = 0.0336)
MVP		0.89
MPC		0.55
ClinPred		0.57	D
GERP RS		5.4
Varity_R		0.11
gMVP		0.28
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1554437349; hg19: chr7-136700406;