10-112950449-GTTTT-GTTTTTT

Variant names:

• chr10-112950449-G-GTT
• rs74804400
• NM_001367943.1:c.-295_-294dupTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001367943.1(TCF7L2):​c.-295_-294dupTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0025 (1 hom., cov: 17)
  • Exomes 𝑓: 0.0068 (0 hom.)
• Consequence: TCF7L2 NM_001367943.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 297 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.-295_-294dupTT		5_prime_UTR_variant	Exon 1 of 15	ENST00000355995.9	NP_001354872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF7L2	ENST00000355995	c.-295_-294dupTT		5_prime_UTR_variant	Exon 1 of 15	1	NM_001367943.1	ENSP00000348274.4

Frequencies

GnomAD3 genomes AF: 0.00247 AC: 298 AN: 120606 Hom.: 1 Cov.: 17

Gnomad AFR AF: 0.00690

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000350

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0121

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000444

Gnomad OTH AF: 0.00188

GnomAD4 exome AF: 0.00678 AC: 502 AN: 74066 Hom.: 0 Cov.: 0 AF XY: 0.00689 AC XY: 255 AN XY: 37012

Gnomad4 AFR exome AF: 0.00588

Gnomad4 AMR exome AF: 0.00938

Gnomad4 ASJ exome AF: 0.00614

Gnomad4 EAS exome AF: 0.00155

Gnomad4 SAS exome AF: 0.00922

Gnomad4 FIN exome AF: 0.00533

Gnomad4 NFE exome AF: 0.00745

Gnomad4 OTH exome AF: 0.00632

GnomAD4 genome AF: 0.00246 AC: 297 AN: 120616 Hom.: 1 Cov.: 17 AF XY: 0.00251 AC XY: 143 AN XY: 56908

Gnomad4 AFR AF: 0.00689

Gnomad4 AMR AF: 0.000350

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0119

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000444

Gnomad4 OTH AF: 0.00188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs74804400; hg19: chr10-114710208;