NM_004613.4:c.11-1618C>A

Variant names:

• chr20-38163217-G-T
• rs7270785
• NM_004613.4:c.11-1618C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

TGM2 Gene-Disease associations (from GenCC):

• type 2 diabetes mellitus

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TGM2	NM_004613.4	c.11-1618C>A		intron_variant	Intron 1 of 12	ENST00000361475.7	NP_004604.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM2	ENST00000361475.7	c.11-1618C>A		intron_variant	Intron 1 of 12	1	NM_004613.4	ENSP00000355330.2

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

African (AFR) AF: 0.200 AC: 8301 AN: 41466

American (AMR) AF: 0.440 AC: 6713 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2084 AN: 3470

East Asian (EAS) AF: 0.417 AC: 2148 AN: 5152

South Asian (SAS) AF: 0.566 AC: 2728 AN: 4820

European-Finnish (FIN) AF: 0.502 AC: 5289 AN: 10546

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.619 AC: 42054 AN: 67898

Other (OTH) AF: 0.512 AC: 1079 AN: 2108

Alfa AF: 0.551 Hom.: 8573

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
PhyloP100		0.18
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: rs7270785; hg19: chr20-36791619;