rs4811528

Variant names:

• chr20-38159027-G-A
• rs4811528
• NM_004613.4:c.190+2393C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004613.4(TGM2):​c.190+2393C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 152,052 control chromosomes in the GnomAD database, including 37,092 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 0.70 (37092 hom., cov: 31)
• Consequence: TGM2 NM_004613.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423
• Publications: 6 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGM2	NM_004613.4	c.190+2393C>T		intron_variant	Intron 2 of 12	ENST00000361475.7	NP_004604.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM2	ENST00000361475.7	c.190+2393C>T		intron_variant	Intron 2 of 12	1	NM_004613.4	ENSP00000355330.2

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105752 AN: 151934 Hom.: 37065 Cov.: 31

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.696

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

GnomAD4 genome AF: 0.696 AC: 105828 AN: 152052 Hom.: 37092 Cov.: 31 AF XY: 0.688 AC XY: 51121 AN XY: 74320

African (AFR) AF: 0.642 AC: 26601 AN: 41422

American (AMR) AF: 0.673 AC: 10276 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2592 AN: 3472

East Asian (EAS) AF: 0.640 AC: 3300 AN: 5160

South Asian (SAS) AF: 0.641 AC: 3090 AN: 4818

European-Finnish (FIN) AF: 0.623 AC: 6587 AN: 10578

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.748 AC: 50844 AN: 68004

Other (OTH) AF: 0.699 AC: 1478 AN: 2114

Alfa AF: 0.710 Hom.: 17894

Bravo AF: 0.699

Asia WGS AF: 0.690 AC: 2399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.75
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4811528; hg19: chr20-36787429;