7-136868746-GCA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001006630.2(CHRM2):c.-502_-501del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 149,326 control chromosomes in the GnomAD database, including 19,264 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (19264 hom., cov: 0)
  • Exomes 𝑓: 0.18 (0 hom.)
• Consequence: CHRM2 NM_001006630.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.214

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 7-136868746-GCA-G is Benign according to our data. Variant chr7-136868746-GCA-G is described in ClinVar as [Benign]. Clinvar id is 1290257.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRM2	NM_001006630.2	c.-502_-501del		5_prime_UTR_variant	1/4	ENST00000680005.1
CHRM2	NM_001006627.3	c.-424_-423del		5_prime_UTR_variant	1/3
CHRM2	NM_001378972.1	c.-614_-613del		5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRM2	ENST00000680005.1	c.-502_-501del		5_prime_UTR_variant	1/4		NM_001006630.2	P1
	ENST00000586239.5	n.274-82857_274-82856del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.503 AC: 74967 AN: 149028 Hom.: 19260 Cov.: 0

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.525

GnomAD4 exome AF: 0.175 AC: 34 AN: 194 Hom.: 0 AF XY: 0.179 AC XY: 29 AN XY: 162

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.503 AC: 74996 AN: 149132 Hom.: 19264 Cov.: 0 AF XY: 0.513 AC XY: 37306 AN XY: 72670

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.795

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.529

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs35916399; hg19: chr7-136553493;