rs2076380

Positions:

• chr20-38165127-G-A
• chr20-38165127-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004613.4(TGM2):​c.10+62C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,612,348 control chromosomes in the GnomAD database, including 94,203 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (8202 hom., cov: 32)
  • Exomes 𝑓: 0.34 (86001 hom.)
• Consequence: TGM2 NM_004613.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12

Genes affected

TGM2 (HGNC:11778): (transglutaminase 2) Transglutaminases are enzymes that catalyze the crosslinking of proteins by epsilon-gamma glutamyl lysine isopeptide bonds. While the primary structure of transglutaminases is not conserved, they all have the same amino acid sequence at their active sites and their activity is calcium-dependent. The protein encoded by this gene acts as a monomer, is induced by retinoic acid, and appears to be involved in apoptosis. Finally, the encoded protein is the autoantigen implicated in celiac disease. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGM2	NM_004613.4	c.10+62C>T		intron_variant		ENST00000361475.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGM2	ENST00000361475.7	c.10+62C>T		intron_variant		1	NM_004613.4	P1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48435 AN: 152000 Hom.: 8202 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.339 AC: 495495 AN: 1460230 Hom.: 86001 AF XY: 0.339 AC XY: 246226 AN XY: 726494

Gnomad4 AFR exome AF: 0.206

Gnomad4 AMR exome AF: 0.446

Gnomad4 ASJ exome AF: 0.269

Gnomad4 EAS exome AF: 0.550

Gnomad4 SAS exome AF: 0.351

Gnomad4 FIN exome AF: 0.435

Gnomad4 NFE exome AF: 0.328

Gnomad4 OTH exome AF: 0.337

GnomAD4 genome AF: 0.318 AC: 48443 AN: 152118 Hom.: 8202 Cov.: 32 AF XY: 0.327 AC XY: 24342 AN XY: 74386

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.292

Alfa AF: 0.259 Hom.: 1040

Bravo AF: 0.311

Asia WGS AF: 0.413 AC: 1435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.74

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: rs2076380; hg19: chr20-36793529; COSMIC: COSV63931375;