rs140171902

Variant names:

• chr20-38138189-G-A
• rs140171902
• NM_004613.4:c.1539C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-38138189-G-A
• chr20-38138189-G-C
• chr20-38138189-G-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_004613.4(TGM2):​c.1539C>T​(p.Thr513Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000249 in 1,608,522 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (1 hom.)
• Consequence: TGM2 NM_004613.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.85
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 20-38138189-G-A is Benign according to our data. Variant chr20-38138189-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 718653.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.85 with no splicing effect.
• BS2: High AC in GnomAd4 at 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGM2	NM_004613.4	c.1539C>T	p.Thr513Thr	synonymous_variant	Exon 10 of 13	ENST00000361475.7	NP_004604.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM2	ENST00000361475.7	c.1539C>T	p.Thr513Thr	synonymous_variant	Exon 10 of 13	1	NM_004613.4	ENSP00000355330.2
TGM2	ENST00000468262.5	n.1623C>T		non_coding_transcript_exon_variant	Exon 10 of 10	1

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000392 AC: 94 AN: 239508 AF XY: 0.000371

Gnomad AFR exome AF: 0.0000660

Gnomad AMR exome AF: 0.000602

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000980

Gnomad NFE exome AF: 0.000602

Gnomad OTH exome AF: 0.000675

GnomAD4 exome AF: 0.000256 AC: 373 AN: 1456220 Hom.: 1 Cov.: 31 AF XY: 0.000247 AC XY: 179 AN XY: 723870

African (AFR) AF: 0.0000300 AC: 1 AN: 33374

American (AMR) AF: 0.000503 AC: 22 AN: 43758

Ashkenazi Jewish (ASJ) AF: 0.0000768 AC: 2 AN: 26032

East Asian (EAS) AF: 0.0000507 AC: 2 AN: 39412

South Asian (SAS) AF: 0.0000469 AC: 4 AN: 85300

European-Finnish (FIN) AF: 0.0000944 AC: 5 AN: 52960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.000292 AC: 324 AN: 1109434

Other (OTH) AF: 0.000216 AC: 13 AN: 60194

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152302 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74480

African (AFR) AF: 0.0000481 AC: 2 AN: 41562

American (AMR) AF: 0.000327 AC: 5 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000411 Hom.: 0

Bravo AF: 0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.44
DANN	Benign	0.61
PhyloP100		-2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs140171902; hg19: chr20-36766591;