2-232531264-GGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCT-GGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCTGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCT

Variant names:

• chr2-232531264-G-GGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCT
• rs530117757
• NM_000751.3:c.821-52_821-18dupGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCT

Variant summary

Our verdict is Uncertain significance. The variant received 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. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 0 publications found

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]

CHRND Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 3A

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• congenital myasthenic syndrome 3B

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Genomics England PanelApp
• congenital myasthenic syndrome 3C

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• lethal multiple pterygium syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• postsynaptic congenital myasthenic syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000751.3. 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
	CHRND	NM_000751.3	MANE Select	c.821-52_821-18dupGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCT		intron	N/A	NP_000742.1
	CHRND	NM_001256657.2		c.776-52_776-18dupGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCT		intron	N/A	NP_001243586.1
	CHRND	NM_001311196.2		c.518-52_518-18dupGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCT		intron	N/A	NP_001298125.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRND	ENST00000258385.8	TSL:1 MANE Select	c.821-88_821-87insGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCT		intron	N/A	ENSP00000258385.3
	CHRND	ENST00000543200.5	TSL:2	c.776-88_776-87insGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCT		intron	N/A	ENSP00000438380.1
	CHRND	ENST00000412233.5	TSL:4	n.510-88_510-87insGGACCCTCTAGGACCGGTGCCCCAAGGTCACAGCT		intron	N/A	ENSP00000398143.1

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

African (AFR) AF: 0.0000467 AC: 1 AN: 21414

American (AMR) AF: 0.0000235 AC: 1 AN: 42566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22020

East Asian (EAS) AF: 0.000166 AC: 6 AN: 36062

South Asian (SAS) AF: 0.000222 AC: 16 AN: 72232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51054

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3832

European-Non Finnish (NFE) AF: 0.0000798 AC: 41 AN: 514028

Other (OTH) AF: 0.0000519 AC: 2 AN: 38510

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

African (AFR) AF: 0.0000728 AC: 3 AN: 41186

American (AMR) AF: 0.000394 AC: 6 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67922

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.000122 Hom.: 199

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs530117757; hg19: chr2-233395974;