rs773330734

chr7-137015838-A-Gchr7-137015838-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001006630.2(CHRM2):c.973A>G(p.Ile325Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I325F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHRM2 NM_001006630.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.32

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23582059).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM2	NM_001006630.2	c.973A>G	p.Ile325Val	missense_variant	4/4	ENST00000680005.1
LOC349160	NR_046103.1	n.341+16956T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM2	ENST00000680005.1	c.973A>G	p.Ile325Val	missense_variant	4/4		NM_001006630.2	P1
	ENST00000586239.5	n.273+16956T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	0.00094	T
BayesDel_noAF	Benign	-0.24
Cadd	Benign	18
Dann	Uncertain	0.97
DEOGEN2	Benign	0.051	T;T;T;T
Eigen	Benign	0.077
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.1	M;M;M;M
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.16	N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.46	T;T;T;T
Sift4G	Benign	0.53	T;T;T;T
Polyphen		0.099	B;B;B;B
Vest4		0.32
MutPred		0.29		Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);Gain of MoRF binding (P = 0.104);
MVP		0.83
MPC		0.62
ClinPred		0.62	D
GERP RS		5.4
Varity_R		0.075
gMVP		0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs773330734; hg19: chr7-136700585;