rs6023526

chr20-38155180-T-Cchr20-38155180-T-G

Variant summary

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

The NM_004613.4(TGM2):c.433+667A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 151,812 control chromosomes in the GnomAD database, including 9,579 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 0.34 (9579 hom., cov: 32)
• Consequence: TGM2 NM_004613.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGM2	NM_004613.4	c.433+667A>G		intron_variant		ENST00000361475.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGM2	ENST00000361475.7	c.433+667A>G		intron_variant		1	NM_004613.4	P1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51265 AN: 151694 Hom.: 9566 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.303

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.338 AC: 51309 AN: 151812 Hom.: 9579 Cov.: 32 AF XY: 0.344 AC XY: 25516 AN XY: 74184

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.300

Alfa AF: 0.168 Hom.: 334

Bravo AF: 0.356

Asia WGS AF: 0.485 AC: 1683 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.014
Dann	Benign	0.49

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: rs6023526; hg19: chr20-36783582;