rs6023526

Variant names:

• chr20-38155180-T-C
• rs6023526
• NM_004613.4:c.433+667A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-38155180-T-C
• chr20-38155180-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.95).
• 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 rank	MANE	Protein	UniProt
TGM2	NM_004613.4	c.433+667A>G		intron_variant	Intron 3 of 12	ENST00000361475.7	NP_004604.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM2	ENST00000361475.7	c.433+667A>G		intron_variant	Intron 3 of 12	1	NM_004613.4	ENSP00000355330.2

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

African (AFR) AF: 0.457 AC: 18888 AN: 41354

American (AMR) AF: 0.396 AC: 6047 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1030 AN: 3466

East Asian (EAS) AF: 0.609 AC: 3142 AN: 5156

South Asian (SAS) AF: 0.421 AC: 2025 AN: 4806

European-Finnish (FIN) AF: 0.242 AC: 2553 AN: 10538

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16579 AN: 67916

Other (OTH) AF: 0.300 AC: 633 AN: 2108

Alfa AF: 0.328 Hom.: 3282

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
PhyloP100		-2.2
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: rs6023526; hg19: chr20-36783582;