2-85133705-GGGCGGCGGCGGCGGC-GGGCGGCGGCGGCGGCGGCGGC

Variant names:

• chr2-85133705-G-GGGCGGC
• rs566806913
• NM_031283.3:c.37_42dupGGCGGC

Variant summary

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

The NM_031283.3(TCF7L1):​c.37_42dupGGCGGC​(p.Gly13_Gly14dup) variant causes a conservative inframe insertion 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 0.0075 (12 hom., cov: 0)
  • Exomes 𝑓: 0.0092 (35 hom.)
• Consequence: TCF7L1 NM_031283.3 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880

Genes affected

TCF7L1 (HGNC:11640): (transcription factor 7 like 1) This gene encodes a member of the T cell factor/lymphoid enhancer factor family of transcription factors. These transcription factors are activated by beta catenin, mediate the Wnt signaling pathway and are antagonized by the transforming growth factor beta signaling pathway. The encoded protein contains a high mobility group-box DNA binding domain and participates in the regulation of cell cycle genes and cellular senescence. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 1101 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L1	NM_031283.3	c.37_42dupGGCGGC	p.Gly13_Gly14dup	conservative_inframe_insertion	Exon 1 of 12	ENST00000282111.4	NP_112573.1
TCF7L1	XM_006712109.3	c.37_42dupGGCGGC	p.Gly13_Gly14dup	conservative_inframe_insertion	Exon 1 of 12		XP_006712172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF7L1	ENST00000282111.4	c.37_42dupGGCGGC	p.Gly13_Gly14dup	conservative_inframe_insertion	Exon 1 of 12	1	NM_031283.3	ENSP00000282111.3

Frequencies

GnomAD3 genomes AF: 0.00755 AC: 1101 AN: 145806 Hom.: 12 Cov.: 0

Gnomad AFR AF: 0.00155

Gnomad AMI AF: 0.00885

Gnomad AMR AF: 0.00156

Gnomad ASJ AF: 0.00207

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000628

Gnomad FIN AF: 0.0411

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00979

Gnomad OTH AF: 0.00248

GnomAD3 exomes AF: 0.00385 AC: 2 AN: 520 Hom.: 0 AF XY: 0.00333 AC XY: 1 AN XY: 300

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00422

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00925 AC: 8608 AN: 930778 Hom.: 35 Cov.: 0 AF XY: 0.00913 AC XY: 3991 AN XY: 437296

Gnomad4 AFR exome AF: 0.000871

Gnomad4 AMR exome AF: 0.00156

Gnomad4 ASJ exome AF: 0.00107

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000609

Gnomad4 FIN exome AF: 0.0124

Gnomad4 NFE exome AF: 0.00999

Gnomad4 OTH exome AF: 0.00586

GnomAD4 genome AF: 0.00755 AC: 1101 AN: 145914 Hom.: 12 Cov.: 0 AF XY: 0.00872 AC XY: 619 AN XY: 70968

Gnomad4 AFR AF: 0.00155

Gnomad4 AMR AF: 0.00156

Gnomad4 ASJ AF: 0.00207

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000629

Gnomad4 FIN AF: 0.0411

Gnomad4 NFE AF: 0.00979

Gnomad4 OTH AF: 0.00245

Bravo AF: 0.00472

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: rs566806913; hg19: chr2-85360828;