chr10-112950748-GA-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PVS1_StrongBS2

The NM_001367943.1(TCF7L2):​c.1delA​(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 0.000284 in 1,529,430 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 29)
Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

TCF7L2
NM_001367943.1 frameshift, start_lost

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 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.
BS2
High AC in GnomAdExome4 at 433 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TCF7L2NM_001367943.1 linkc.1delA 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
TCF7L2ENST00000355995.9 linkc.1delA p.Met1fs frameshift_variant, start_lost Exon 1 of 15 1 NM_001367943.1 ENSP00000348274.4 Q9NQB0-1

Frequencies

GnomAD3 genomes
AF:
0.00000668
AC:
1
AN:
149776
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000212
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000314
AC:
433
AN:
1379554
Hom.:
0
Cov.:
32
AF XY:
0.000317
AC XY:
216
AN XY:
680600
show subpopulations
Gnomad4 AFR exome
AF:
0.000996
Gnomad4 AMR exome
AF:
0.00241
Gnomad4 ASJ exome
AF:
0.000572
Gnomad4 EAS exome
AF:
0.000906
Gnomad4 SAS exome
AF:
0.000614
Gnomad4 FIN exome
AF:
0.000286
Gnomad4 NFE exome
AF:
0.000178
Gnomad4 OTH exome
AF:
0.000405
GnomAD4 genome
AF:
0.00000667
AC:
1
AN:
149876
Hom.:
0
Cov.:
29
AF XY:
0.0000137
AC XY:
1
AN XY:
73128
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000213
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00464
Hom.:
0

ClinVar

Not reported in ClinVar

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.

Other links and lift over

dbSNP: rs373426839; hg19: chr10-114710507; API