2-85133705-GGGCGGCGGCGGCGGC-GGGCGGCGGCGGCGGCGGC

Variant names:

• chr2-85133705-G-GGGC
• rs566806913
• NM_031283.3:c.40_42dupGGC

Variant summary

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

The NM_031283.3(TCF7L1):​c.40_42dupGGC​(p.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 0.00014 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00013 (0 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 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF7L1	NM_031283.3	c.40_42dupGGC	p.Gly14dup	conservative_inframe_insertion	Exon 1 of 12	ENST00000282111.4	NP_112573.1
TCF7L1	XM_006712109.3	c.40_42dupGGC	p.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.40_42dupGGC	p.Gly14dup	conservative_inframe_insertion	Exon 1 of 12	1	NM_031283.3	ENSP00000282111.3

Frequencies

GnomAD3 genomes AF: 0.000144 AC: 21 AN: 145814 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000740

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000340

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000400

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.000118

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000137

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000126 AC: 117 AN: 930918 Hom.: 0 Cov.: 0 AF XY: 0.000123 AC XY: 54 AN XY: 437368

Gnomad4 AFR exome AF: 0.0000544

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000277

Gnomad4 FIN exome AF: 0.0000855

Gnomad4 NFE exome AF: 0.000129

Gnomad4 OTH exome AF: 0.0000598

GnomAD4 genome AF: 0.000144 AC: 21 AN: 145814 Hom.: 0 Cov.: 0 AF XY: 0.000155 AC XY: 11 AN XY: 70850

Gnomad4 AFR AF: 0.0000740

Gnomad4 AMR AF: 0.000340

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000400

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.000118

Gnomad4 NFE AF: 0.000137

Gnomad4 OTH AF: 0.00

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;