2-232531264-GGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCT-GGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCTGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCT

Position:

• chr2-232531264-GGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCT-GGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCTGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCT

Variant summary

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

The NM_000751.3(CHRND):​c.821-52_821-18dupGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000892 in 953,304 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 0.00012 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000084 (0 hom.)
• Consequence: CHRND NM_000751.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301

Genes affected

CHRND (HGNC:1965): (cholinergic receptor nicotinic delta subunit) The acetylcholine receptor of muscle has 5 subunits of 4 different types: 2 alpha and 1 each of beta, gamma and delta subunits. After acetylcholine binding, the receptor undergoes an extensive conformation change that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. Defects in this gene are a cause of multiple pterygium syndrome lethal type (MUPSL), congenital myasthenic syndrome slow-channel type (SCCMS), and congenital myasthenic syndrome fast-channel type (FCCMS). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRND	NM_000751.3	c.821-52_821-18dupGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCT		intron_variant		ENST00000258385.8	NP_000742.1
CHRND	NM_001256657.2	c.776-52_776-18dupGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCT		intron_variant			NP_001243586.1
CHRND	NM_001311196.2	c.518-52_518-18dupGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCT		intron_variant			NP_001298125.1
CHRND	NM_001311195.2	c.239-52_239-18dupGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCT		intron_variant			NP_001298124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRND	ENST00000258385.8	c.821-88_821-87insGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCT		intron_variant		1	NM_000751.3	ENSP00000258385.3

Frequencies

GnomAD3 genomes AF: 0.000119 AC: 18 AN: 151586 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000728

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000394

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000836 AC: 67 AN: 801718 Hom.: 0 AF XY: 0.0000969 AC XY: 41 AN XY: 423314

Gnomad4 AFR exome AF: 0.0000467

Gnomad4 AMR exome AF: 0.0000235

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000166

Gnomad4 SAS exome AF: 0.000222

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000798

Gnomad4 OTH exome AF: 0.0000519

GnomAD4 genome AF: 0.000119 AC: 18 AN: 151586 Hom.: 0 Cov.: 28 AF XY: 0.000135 AC XY: 10 AN XY: 73992

Gnomad4 AFR AF: 0.0000728

Gnomad4 AMR AF: 0.000394

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

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: rs530117757; hg19: chr2-233395974;