dbSNP rs2076380: TGM2:c.10+62C>T (chr20-38165127-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004613.4(TGM2):c.10+62C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,612,348 control chromosomes in the GnomAD database, including 94,203 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 0.32 ( 8202 hom., cov: 32)

Exomes 𝑓: 0.34 ( 86001 hom. )

Consequence

TGM2
NM_004613.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.12

Publications

11 publications found

Variant links:

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

TGM2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGM2	NM_004613.4 link	c.10+62C>T		intron_variant	Intron 1 of 12	ENST00000361475.7	NP_004604.2	P21980-1V9HWG3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM2	ENST00000361475.7 link	c.10+62C>T		intron_variant	Intron 1 of 12	1	NM_004613.4	ENSP00000355330.2		P21980-1

Frequencies

GnomAD3 genomes

AF:

0.319

AC:

48435

AN:

152000

Hom.:

8202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.393

Gnomad AMR

AF:

0.376

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.535

Gnomad SAS

AF:

0.358

Gnomad FIN

AF:

0.449

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.296

GnomAD4 exome

AF:

0.339

AC:

495495

AN:

1460230

Hom.:

86001

AF XY:

0.339

AC XY:

246226

AN XY:

726494

show subpopulations

African (AFR)

AF:

0.206

AC:

6893

AN:

33458

American (AMR)

AF:

0.446

AC:

19922

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

7012

AN:

26114

East Asian (EAS)

AF:

0.550

AC:

21831

AN:

39674

South Asian (SAS)

AF:

0.351

AC:

30257

AN:

86212

European-Finnish (FIN)

AF:

0.435

AC:

23176

AN:

53294

Middle Eastern (MID)

AF:

0.270

AC:

1559

AN:

5764

European-Non Finnish (NFE)

AF:

0.328

AC:

364517

AN:

1110760

Other (OTH)

AF:

0.337

AC:

20328

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

17514

35028

52541

70055

87569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.318

AC:

48443

AN:

152118

Hom.:

8202

Cov.:

AF XY:

0.327

AC XY:

24342

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.215

AC:

8911

AN:

41508

American (AMR)

AF:

0.376

AC:

5754

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

967

AN:

3468

East Asian (EAS)

AF:

0.535

AC:

2765

AN:

5164

South Asian (SAS)

AF:

0.356

AC:

1720

AN:

4826

European-Finnish (FIN)

AF:

0.449

AC:

4756

AN:

10584

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.331

AC:

22528

AN:

67964

Other (OTH)

AF:

0.292

AC:

616

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1657

3313

4970

6626

8283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.318

Hom.:

13005

Bravo

AF:

0.311

Asia WGS

AF:

0.413

AC:

1435

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.11

(source)

DANN

Benign

0.74

PhyloP100

-2.1

PromoterAI

-0.038

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs2076380

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over