2-232526234-A-T

Variant names:

• chr2-232526234-A-T
• rs1691455697
• NM_000751.3:c.19A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000751.3(CHRND):​c.19A>T​(p.Thr7Ser) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHRND NM_000751.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.685

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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09576696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRND	NM_000751.3	c.19A>T	p.Thr7Ser	missense_variant	Exon 1 of 12	ENST00000258385.8	NP_000742.1
CHRND	NM_001256657.2	c.19A>T	p.Thr7Ser	missense_variant	Exon 1 of 11		NP_001243586.1
CHRND	NM_001311196.2	c.-253A>T		5_prime_UTR_variant	Exon 1 of 12		NP_001298125.1
CHRND	NM_001311195.2	c.-253A>T		5_prime_UTR_variant	Exon 1 of 10		NP_001298124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRND	ENST00000258385.8	c.19A>T	p.Thr7Ser	missense_variant	Exon 1 of 12	1	NM_000751.3	ENSP00000258385.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.90
DEOGEN2	Benign	0.091	.;.;T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.36	T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.096	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.27	.;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.51	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.33	T;T;T
Sift4G	Benign	0.84	T;T;T
Polyphen		0.0	.;.;B
Vest4		0.14, 0.12
MutPred		0.48		Gain of disorder (P = 0.0678);Gain of disorder (P = 0.0678);Gain of disorder (P = 0.0678);
MVP		0.69
MPC		0.22
ClinPred		0.089	T
GERP RS		0.78
Varity_R		0.050
gMVP		0.43

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

Other links and lift over

dbSNP: rs1691455697; hg19: chr2-233390944;