rs2767

Variant names:

• chr2-232535364-A-G
• rs2767
• NM_000751.3:c.*52A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-232535364-A-G
• chr2-232535364-A-C
• chr2-232535364-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000751.3(CHRND):​c.*52A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,597,770 control chromosomes in the GnomAD database, including 115,240 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10308 hom., cov: 32)
  • Exomes 𝑓: 0.37 (104932 hom.)
• Consequence: CHRND NM_000751.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.936
• Publications: 25 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• congenital myasthenic syndrome 3B

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

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

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 2-232535364-A-G is Benign according to our data. Variant chr2-232535364-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 334975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRND	NM_000751.3	MANE Select	c.*52A>G		3_prime_UTR	Exon 12 of 12	NP_000742.1	Q07001-1
	CHRND	NM_001256657.2		c.*52A>G		3_prime_UTR	Exon 11 of 11	NP_001243586.1	Q07001-2
	CHRND	NM_001311196.2		c.*52A>G		3_prime_UTR	Exon 12 of 12	NP_001298125.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRND	ENST00000258385.8	TSL:1 MANE Select	c.*52A>G		3_prime_UTR	Exon 12 of 12	ENSP00000258385.3	Q07001-1
	CHRND	ENST00000543200.5	TSL:2	c.*52A>G		3_prime_UTR	Exon 11 of 11	ENSP00000438380.1	Q07001-2
	CHRND	ENST00000955151.1		c.*52A>G		3_prime_UTR	Exon 11 of 11	ENSP00000625210.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54369 AN: 151962 Hom.: 10286 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.369

GnomAD2 exomes AF: 0.417 AC: 100435 AN: 241134 AF XY: 0.411

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.627

Gnomad ASJ exome AF: 0.372

Gnomad EAS exome AF: 0.553

Gnomad FIN exome AF: 0.339

Gnomad NFE exome AF: 0.361

Gnomad OTH exome AF: 0.397

GnomAD4 exome AF: 0.375 AC: 541608 AN: 1445690 Hom.: 104932 Cov.: 30 AF XY: 0.376 AC XY: 270566 AN XY: 719930

African (AFR) AF: 0.266 AC: 8864 AN: 33332

American (AMR) AF: 0.615 AC: 27473 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 9711 AN: 26100

East Asian (EAS) AF: 0.558 AC: 22119 AN: 39658

South Asian (SAS) AF: 0.434 AC: 37376 AN: 86102

European-Finnish (FIN) AF: 0.335 AC: 14629 AN: 43668

Middle Eastern (MID) AF: 0.349 AC: 1989 AN: 5706

European-Non Finnish (NFE) AF: 0.359 AC: 396707 AN: 1106358

Other (OTH) AF: 0.378 AC: 22740 AN: 60126

GnomAD4 genome AF: 0.358 AC: 54429 AN: 152080 Hom.: 10308 Cov.: 32 AF XY: 0.360 AC XY: 26776 AN XY: 74342

African (AFR) AF: 0.280 AC: 11607 AN: 41472

American (AMR) AF: 0.500 AC: 7640 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1253 AN: 3470

East Asian (EAS) AF: 0.548 AC: 2834 AN: 5168

South Asian (SAS) AF: 0.431 AC: 2074 AN: 4816

European-Finnish (FIN) AF: 0.331 AC: 3504 AN: 10598

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24253 AN: 67958

Other (OTH) AF: 0.375 AC: 790 AN: 2108

Alfa AF: 0.366 Hom.: 25735

Bravo AF: 0.372

Asia WGS AF: 0.522 AC: 1815 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Autosomal recessive multiple pterygium syndrome (2)
-	-	2	not provided (2)
-	-	1	Congenital myasthenic syndrome (1)
-	-	1	Congenital Myasthenic Syndrome, Dominant/Recessive (1)
-	-	1	Lethal multiple pterygium syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.61
DANN	Benign	0.29
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2767; hg19: chr2-233400074; COSMIC: COSV51318184; COSMIC: COSV51318184;