2-232545793-T-C

Variant names:

• chr2-232545793-T-C
• rs11690038
• NM_145702.4:c.*2314A>G

Variant summary

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

The NM_145702.4(TIGD1):​c.*2314A>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 0.0234 in 1,512,122 control chromosomes in the GnomAD database, including 764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (87 hom., cov: 32)
  • Exomes 𝑓: 0.023 (677 hom.)
• Consequence: TIGD1 NM_145702.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.420
• Publications: 10 publications found

Genes affected

TIGD1 (HGNC:14523): (tigger transposable element derived 1) The protein encoded by this gene belongs to the tigger subfamily of the pogo superfamily of DNA-mediated transposons in humans. These proteins are related to DNA transposons found in fungi and nematodes, and more distantly to the Tc1 and mariner transposases. They are also very similar to the major mammalian centromere protein B. The exact function of this gene is not known. [provided by RefSeq, Jul 2008]

CHRNG (HGNC:1967): (cholinergic receptor nicotinic gamma subunit) The mammalian muscle-type acetylcholine receptor is a transmembrane pentameric glycoprotein with two alpha subunits, one beta, one delta, and one epsilon (in adult skeletal muscle) or gamma (in fetal and denervated muscle) subunit. This gene, which encodes the gamma subunit, is expressed prior to the thirty-third week of gestation in humans. The gamma subunit of the acetylcholine receptor plays a role in neuromuscular organogenesis and ligand binding and disruption of gamma subunit expression prevents the correct localization of the receptor in cell membranes. Mutations in this gene cause Escobar syndrome and a lethal form of multiple pterygium syndrome. Muscle-type acetylcholine receptor is the major antigen in the autoimmune disease myasthenia gravis.[provided by RefSeq, Sep 2009]

CHRNG Gene-Disease associations (from GenCC):

• autosomal recessive multiple pterygium syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet
• CHRNG-associated hypo-akinesia disorder of prenatal onset

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• lethal multiple pterygium syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• transient neonatal myasthenia gravis

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-232545793-T-C is Benign according to our data. Variant chr2-232545793-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 335017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0962 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145702.4. 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
	TIGD1	NM_145702.4	MANE Select	c.*2314A>G		3_prime_UTR	Exon 1 of 1	NP_663748.1	Q96MW7
	CHRNG	NM_005199.5	MANE Select	c.*77T>C		3_prime_UTR	Exon 12 of 12	NP_005190.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIGD1	ENST00000408957.7	TSL:6 MANE Select	c.*2314A>G		3_prime_UTR	Exon 1 of 1	ENSP00000386186.3	Q96MW7
	CHRNG	ENST00000651502.1	MANE Select	c.*77T>C		3_prime_UTR	Exon 12 of 12	ENSP00000498757.1	P07510-1
	CHRNG	ENST00000389492.3	TSL:1	c.*77T>C		downstream_gene	N/A	ENSP00000374143.3	P07510-2

Frequencies

GnomAD3 genomes AF: 0.0230 AC: 3502 AN: 152168 Hom.: 88 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0431

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.0332

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0182

Gnomad OTH AF: 0.0292

GnomAD4 exome AF: 0.0235 AC: 31895 AN: 1359836 Hom.: 677 Cov.: 22 AF XY: 0.0235 AC XY: 16024 AN XY: 682444

African (AFR) AF: 0.0101 AC: 319 AN: 31544

American (AMR) AF: 0.0646 AC: 2868 AN: 44414

Ashkenazi Jewish (ASJ) AF: 0.00706 AC: 180 AN: 25492

East Asian (EAS) AF: 0.106 AC: 4164 AN: 39220

South Asian (SAS) AF: 0.0288 AC: 2428 AN: 84188

European-Finnish (FIN) AF: 0.0327 AC: 1607 AN: 49182

Middle Eastern (MID) AF: 0.0201 AC: 112 AN: 5580

European-Non Finnish (NFE) AF: 0.0182 AC: 18655 AN: 1023146

Other (OTH) AF: 0.0274 AC: 1562 AN: 57070

GnomAD4 genome AF: 0.0230 AC: 3504 AN: 152286 Hom.: 87 Cov.: 32 AF XY: 0.0238 AC XY: 1775 AN XY: 74470

African (AFR) AF: 0.0118 AC: 490 AN: 41562

American (AMR) AF: 0.0431 AC: 659 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3470

East Asian (EAS) AF: 0.103 AC: 535 AN: 5174

South Asian (SAS) AF: 0.0300 AC: 145 AN: 4830

European-Finnish (FIN) AF: 0.0332 AC: 352 AN: 10612

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0182 AC: 1237 AN: 68018

Other (OTH) AF: 0.0293 AC: 62 AN: 2114

Alfa AF: 0.0211 Hom.: 78

Bravo AF: 0.0245

Asia WGS AF: 0.0490 AC: 170 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal recessive multiple pterygium syndrome (1)
-	-	1	Lethal multiple pterygium syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.32
PhyloP100		-0.42
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: rs11690038; hg19: chr2-233410503; COSMIC: COSV51472422; COSMIC: COSV51472422;