rs7270785

Positions:

• chr20-38163217-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.11-1618C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,932 control chromosomes in the GnomAD database, including 19,121 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 0.47 (19121 hom., cov: 31)
• Consequence: TGM2 NM_004613.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGM2	NM_004613.4	c.11-1618C>A		intron_variant		ENST00000361475.7	NP_004604.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGM2	ENST00000361475.7	c.11-1618C>A		intron_variant		1	NM_004613.4	ENSP00000355330	P1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71078 AN: 151814 Hom.: 19118 Cov.: 31

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.468 AC: 71092 AN: 151932 Hom.: 19121 Cov.: 31 AF XY: 0.463 AC XY: 34348 AN XY: 74244

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.512

Alfa AF: 0.556 Hom.: 6892

Bravo AF: 0.450

Asia WGS AF: 0.497 AC: 1731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.62

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: rs7270785; hg19: chr20-36791619;