7-137016054-A-G

Variant names:

• chr7-137016054-A-G
• rs745902607
• NM_001006630.2:c.1189A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001006630.2(CHRM2):​c.1189A>G​(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. 14/22 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: 0.000042 (0 hom.)
• Consequence: CHRM2 NM_001006630.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.32
• Publications: 1 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.23536927).

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.1189A>G	p.Ile397Val	missense	Exon 4 of 4	NP_001006631.1	P08172
	CHRM2	NM_000739.3		c.1189A>G	p.Ile397Val	missense	Exon 4 of 4	NP_000730.1	P08172
	CHRM2	NM_001006626.3		c.1189A>G	p.Ile397Val	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.1189A>G	p.Ile397Val	missense	Exon 4 of 4	ENSP00000505686.1	P08172
	CHRM2	ENST00000320658.9	TSL:1	c.1189A>G	p.Ile397Val	missense	Exon 3 of 3	ENSP00000319984.5	P08172
	CHRM2	ENST00000401861.1	TSL:1	c.1189A>G	p.Ile397Val	missense	Exon 5 of 5	ENSP00000384401.1	P08172

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000400 AC: 10 AN: 250298 AF XY: 0.0000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000424 AC: 62 AN: 1460718 Hom.: 0 Cov.: 31 AF XY: 0.0000509 AC XY: 37 AN XY: 726722

African (AFR) AF: 0.0000300 AC: 1 AN: 33330

American (AMR) AF: 0.00 AC: 0 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.000983 AC: 39 AN: 39664

South Asian (SAS) AF: 0.000255 AC: 22 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111386

Other (OTH) AF: 0.00 AC: 0 AN: 60304

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.076
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.41	N
PhyloP100		7.3
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.19
Sift	Benign	0.10	T
Sift4G	Benign	0.17	T
Polyphen		0.041	B
Vest4		0.20
MutPred		0.57		Gain of sheet (P = 0.0827)
MVP		0.90
MPC		0.54
ClinPred		0.18	T
GERP RS		5.9
Varity_R		0.27
gMVP		0.36
Mutation Taster		=56/44	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: rs745902607; hg19: chr7-136700801;