NM_001006630.2:c.-502_-501dupCA

Variant names:

• chr7-136868746-G-GCA
• rs35916399
• NM_001006630.2:c.-502_-501dupCA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001006630.2(CHRM2):​c.-502_-501dupCA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.020 (44 hom., cov: 0)
  • Exomes 𝑓: 0.0051 (0 hom.)
• Consequence: CHRM2 NM_001006630.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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]

ENSG00000234352 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0199 (2969/149360) while in subpopulation AFR AF= 0.0486 (1984/40792). AF 95% confidence interval is 0.0469. There are 44 homozygotes in gnomad4. There are 1342 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 44 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-502_-501dupCA		5_prime_UTR_variant	Exon 1 of 4	ENST00000680005.1	NP_001006631.1
CHRM2	NM_001006627.3	c.-424_-423dupCA		5_prime_UTR_variant	Exon 1 of 3		NP_001006628.1
CHRM2	NM_001378972.1	c.-614_-613dupCA		5_prime_UTR_variant	Exon 1 of 5		NP_001365901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005	c.-502_-501dupCA		5_prime_UTR_variant	Exon 1 of 4		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2946 AN: 149254 Hom.: 45 Cov.: 0

Gnomad AFR AF: 0.0483

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.00959

Gnomad ASJ AF: 0.0102

Gnomad EAS AF: 0.0132

Gnomad SAS AF: 0.00469

Gnomad FIN AF: 0.000792

Gnomad MID AF: 0.00662

Gnomad NFE AF: 0.00940

Gnomad OTH AF: 0.0214

GnomAD4 exome AF: 0.00510 AC: 1 AN: 196 Hom.: 0 Cov.: 0 AF XY: 0.00610 AC XY: 1 AN XY: 164

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00575

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0199 AC: 2969 AN: 149360 Hom.: 44 Cov.: 0 AF XY: 0.0184 AC XY: 1342 AN XY: 72792

Gnomad4 AFR AF: 0.0486

Gnomad4 AMR AF: 0.00958

Gnomad4 ASJ AF: 0.0102

Gnomad4 EAS AF: 0.0136

Gnomad4 SAS AF: 0.00470

Gnomad4 FIN AF: 0.000792

Gnomad4 NFE AF: 0.00940

Gnomad4 OTH AF: 0.0217

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;