2-232535364-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.936

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 334975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-232535364-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CHRND	NM_000751.3 link	c.*52A>G	3_prime_UTR_variant	Exon 12 of 12	ENST00000258385.8	NP_000742.1	Q07001-1
CHRND	NM_001256657.2 link	c.*52A>G	3_prime_UTR_variant	Exon 11 of 11		NP_001243586.1	Q07001-2
CHRND	NM_001311196.2 link	c.*52A>G	3_prime_UTR_variant	Exon 12 of 12		NP_001298125.1	Q07001
CHRND	NM_001311195.2 link	c.*52A>G	3_prime_UTR_variant	Exon 10 of 10		NP_001298124.1	Q07001B4E3W4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRND	ENST00000258385.8 link	c.*52A>G		3_prime_UTR_variant	Exon 12 of 12	1	NM_000751.3	ENSP00000258385.3		Q07001-1

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

54369

AN:

151962

Hom.:

10286

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.417

AC:

100435

AN:

241134

Hom.:

22372

AF XY:

0.411

AC XY:

53959

AN XY:

131204

show subpopulations

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 SAS exome

AF:

0.429

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.:

AF XY:

0.376

AC XY:

270566

AN XY:

719930

show subpopulations

Gnomad4 AFR exome

AF:

0.266

Gnomad4 AMR exome

AF:

0.615

Gnomad4 ASJ exome

AF:

0.372

Gnomad4 EAS exome

AF:

0.558

Gnomad4 SAS exome

AF:

0.434

Gnomad4 FIN exome

AF:

0.335

Gnomad4 NFE exome

AF:

0.359

Gnomad4 OTH exome

AF:

0.378

GnomAD4 genome

AF:

0.358

AC:

54429

AN:

152080

Hom.:

10308

Cov.:

AF XY:

0.360

AC XY:

26776

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.280

Gnomad4 AMR

AF:

0.500

Gnomad4 ASJ

AF:

0.361

Gnomad4 EAS

AF:

0.548

Gnomad4 SAS

AF:

0.431

Gnomad4 FIN

AF:

0.331

Gnomad4 NFE

AF:

0.357

Gnomad4 OTH

AF:

0.375

Alfa

AF:

0.358

Hom.:

13265

Bravo

AF:

0.372

Asia WGS

AF:

0.522

AC:

1815

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal recessive multiple pterygium syndrome

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Jun 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Congenital Myasthenic Syndrome, Dominant/Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Lethal multiple pterygium syndrome

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Congenital myasthenic syndrome

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.61

DANN

Benign

0.29

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over