Variant chr10-112950748-G-GA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 4P and 9B. PVS1_StrongBP6BS1BS2

The NM_001367943.1(TCF7L2):c.1dupA(p.Met1fs) variant causes a frameshift, start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,533,132 control chromosomes in the GnomAD database, including 61 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.010 ( 24 hom., cov: 29)

Exomes 𝑓: 0.0017 ( 37 hom. )

Consequence

TCF7L2
NM_001367943.1 frameshift, start_lost

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1O:1

Conservation

PhyloP100: 1.35

Variant links:

Genes affected

TCF7L2 (HGNC:11641): (transcription factor 7 like 2) This gene encodes a high mobility group (HMG) box-containing transcription factor that plays a key role in the Wnt signaling pathway. The protein has been implicated in blood glucose homeostasis. Genetic variants of this gene are associated with increased risk of type 2 diabetes. Several transcript variants encoding multiple different isoforms have been found for this gene.[provided by RefSeq, Oct 2010]

TCF7L2 links:

ENSG00000233547 (HGNC:):

ENSG00000233547 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.999 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

BP6

Variant 10-112950748-G-GA is Benign according to our data. Variant chr10-112950748-G-GA is described in ClinVar as [Benign]. Clinvar id is 3257944.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0102 (1529/149880) while in subpopulation AFR AF= 0.0337 (1375/40810). AF 95% confidence interval is 0.0322. There are 24 homozygotes in gnomad4. There are 728 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1529 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L2	NM_001367943.1 link	c.1dupA	p.Met1fs	frameshift_variant, start_lost	Exon 1 of 15	ENST00000355995.9	NP_001354872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF7L2	ENST00000355995.9 link	c.1dupA	p.Met1fs	frameshift_variant, start_lost	Exon 1 of 15	1	NM_001367943.1	ENSP00000348274.4		Q9NQB0-1

Frequencies

GnomAD3 genomes

AF:

0.0102

AC:

1528

AN:

149780

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00565

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00741

Gnomad SAS

AF:

0.000212

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000134

Gnomad OTH

AF:

0.0102

GnomAD3 exomes

AF:

0.00364

AC:

447

AN:

122762

Hom.:

AF XY:

0.00296

AC XY:

194

AN XY:

65550

show subpopulations

Gnomad AFR exome

AF:

0.0408

Gnomad AMR exome

AF:

0.00372

Gnomad ASJ exome

AF:

0.000777

Gnomad EAS exome

AF:

0.00400

Gnomad SAS exome

AF:

0.000465

Gnomad FIN exome

AF:

0.000137

Gnomad NFE exome

AF:

0.000783

Gnomad OTH exome

AF:

0.00209

GnomAD4 exome

AF:

0.00170

AC:

2348

AN:

1383252

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

1096

AN XY:

682506

show subpopulations

Gnomad4 AFR exome

AF:

0.0330

Gnomad4 AMR exome

AF:

0.00259

Gnomad4 ASJ exome

AF:

0.000122

Gnomad4 EAS exome

AF:

0.0224

Gnomad4 SAS exome

AF:

0.000494

Gnomad4 FIN exome

AF:

0.0000203

Gnomad4 NFE exome

AF:

0.000216

Gnomad4 OTH exome

AF:

0.00244

GnomAD4 genome

AF:

0.0102

AC:

1529

AN:

149880

Hom.:

Cov.:

AF XY:

0.00995

AC XY:

728

AN XY:

73134

show subpopulations

Gnomad4 AFR

AF:

0.0337

Gnomad4 AMR

AF:

0.00564

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00743

Gnomad4 SAS

AF:

0.000213

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000134

Gnomad4 OTH

AF:

0.0101

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TCF7L2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 31, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Neoplasm

Other:1

-, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Mar 04, 2025

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over