chr10-112951893-A-AGG

Variant names:

• chr10-112951893-A-AGG
• rs55688545
• NM_001367943.1:c.381+293_381+294dupGG

Variant summary

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

The NM_001367943.1(TCF7L2):​c.381+293_381+294dupGG variant causes a intron 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 0.00088 (1 hom., cov: 20)
  • Exomes 𝑓: 0.00075 (0 hom.)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.508

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]

LOC124902502 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 124 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.381+293_381+294dupGG		intron_variant	Intron 3 of 14	ENST00000355995.9	NP_001354872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF7L2	ENST00000355995.9	c.381+286_381+287insGG		intron_variant	Intron 3 of 14	1	NM_001367943.1	ENSP00000348274.4

Frequencies

GnomAD3 genomes AF: 0.000876 AC: 124 AN: 141512 Hom.: 1 Cov.: 20

Gnomad AFR AF: 0.000282

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000758

Gnomad ASJ AF: 0.00241

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00182

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0161

Gnomad NFE AF: 0.00112

Gnomad OTH AF: 0.00418

GnomAD4 exome AF: 0.000745 AC: 1 AN: 1342 Hom.: 0 Cov.: 0 AF XY: 0.00119 AC XY: 1 AN XY: 840

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00112

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.000876 AC: 124 AN: 141610 Hom.: 1 Cov.: 20 AF XY: 0.000768 AC XY: 53 AN XY: 68978

Gnomad4 AFR AF: 0.000281

Gnomad4 AMR AF: 0.000757

Gnomad4 ASJ AF: 0.00241

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00182

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00112

Gnomad4 OTH AF: 0.00413

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: rs55688545; hg19: chr10-114711652;