rs1553575402

Positions:

• chr2-232534116-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The ENST00000258385.8(CHRND):​c.1233C>T​(p.Ala411=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CHRND ENST00000258385.8 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.67

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 2-232534116-C-T is Benign according to our data. Variant chr2-232534116-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 534535.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.67 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRND	NM_000751.3	c.1233C>T	p.Ala411=	synonymous_variant	10/12	ENST00000258385.8	NP_000742.1
CHRND	NM_001256657.2	c.1188C>T	p.Ala396=	synonymous_variant	9/11		NP_001243586.1
CHRND	NM_001311196.2	c.930C>T	p.Ala310=	synonymous_variant	10/12		NP_001298125.1
CHRND	NM_001311195.2	c.651C>T	p.Ala217=	synonymous_variant	8/10		NP_001298124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRND	ENST00000258385.8	c.1233C>T	p.Ala411=	synonymous_variant	10/12	1	NM_000751.3	ENSP00000258385	P1
CHRND	ENST00000543200.5	c.1188C>T	p.Ala396=	synonymous_variant	9/11	2		ENSP00000438380
CHRND	ENST00000441621.6	c.*415C>T		3_prime_UTR_variant, NMD_transcript_variant	9/11	5		ENSP00000408819
CHRND	ENST00000446616.1	c.*874C>T		3_prime_UTR_variant, NMD_transcript_variant	10/12	3		ENSP00000410801

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Lethal multiple pterygium syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 03, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	11
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs1553575402; hg19: chr2-233398826;