7-136868746-GCACACACACACACACA-GCACACACA

Variant names:

• chr7-136868746-GCACACACA-G
• rs35916399
• NM_001006630.2:c.-508_-501delCACACACA

Variant summary

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

The NM_001006630.2(CHRM2):​c.-508_-501delCACACACA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000669 in 149,568 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000060 (0 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: 3.33

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-508_-501delCACACACA		5_prime_UTR_variant	Exon 1 of 4	ENST00000680005.1	NP_001006631.1
CHRM2	NM_001006627.3	c.-430_-423delCACACACA		5_prime_UTR_variant	Exon 1 of 3		NP_001006628.1
CHRM2	NM_001378972.1	c.-620_-613delCACACACA		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.-508_-501delCACACACA		5_prime_UTR_variant	Exon 1 of 4		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.0000603 AC: 9 AN: 149266 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000990

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000104

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00510 AC: 1 AN: 196 Hom.: 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: 0.0000603 AC: 9 AN: 149372 Hom.: 0 Cov.: 0 AF XY: 0.0000824 AC XY: 6 AN XY: 72804

Gnomad4 AFR AF: 0.0000245

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000990

Gnomad4 NFE AF: 0.000104

Gnomad4 OTH AF: 0.00

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;