7-137015895-G-C

Variant names:

• chr7-137015895-G-C
• rs201165506
• NM_001006630.2:c.1030G>C

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.1030G>C​(p.Val344Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. V344G) 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: 9.94
• Publications: 6 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=0.1903058).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	NM_001006630.2	MANE Select	c.1030G>C	p.Val344Leu	missense	Exon 4 of 4	NP_001006631.1
	CHRM2	NM_000739.3		c.1030G>C	p.Val344Leu	missense	Exon 4 of 4	NP_000730.1
	CHRM2	NM_001006626.3		c.1030G>C	p.Val344Leu	missense	Exon 5 of 5	NP_001006627.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRM2	ENST00000680005.1	MANE Select	c.1030G>C	p.Val344Leu	missense	Exon 4 of 4	ENSP00000505686.1
	CHRM2	ENST00000320658.9	TSL:1	c.1030G>C	p.Val344Leu	missense	Exon 3 of 3	ENSP00000319984.5
	CHRM2	ENST00000401861.1	TSL:1	c.1030G>C	p.Val344Leu	missense	Exon 5 of 5	ENSP00000384401.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.058	T
Eigen	Benign	0.078
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L
PhyloP100		9.9
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.13
Sift	Benign	0.62	T
Sift4G	Benign	0.58	T
Polyphen		0.0020	B
Vest4		0.30
MutPred		0.31		Loss of glycosylation at T343 (P = 0.08)
MVP		0.67
MPC		0.57
ClinPred		0.73	D
GERP RS		5.4
Varity_R		0.20
gMVP		0.49
Mutation Taster		=25/75	disease causing

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: rs201165506; hg19: chr7-136700642;