2-85133705-GGGCGGCGGCGGCGGC-GGGCGGCGGCGGCGGCGGCGGCGGCGGC

Variant names:

• chr2-85133705-G-GGGCGGCGGCGGC
• rs566806913
• NM_031283.3:c.31_42dupGGCGGCGGCGGC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_031283.3(TCF7L1):​c.31_42dupGGCGGCGGCGGC​(p.Gly11_Gly14dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000032 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TCF7L1 NM_031283.3 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880
• Publications: 5 publications found

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]

TCF7L1 Gene-Disease associations (from GenCC):

• combined pituitary hormone deficiencies, genetic form

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

ENSG00000300535 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031283.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7L1	NM_031283.3	MANE Select	c.31_42dupGGCGGCGGCGGC	p.Gly11_Gly14dup	conservative_inframe_insertion	Exon 1 of 12	NP_112573.1	Q9HCS4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7L1	ENST00000282111.4	TSL:1 MANE Select	c.31_42dupGGCGGCGGCGGC	p.Gly11_Gly14dup	conservative_inframe_insertion	Exon 1 of 12	ENSP00000282111.3	Q9HCS4
	TCF7L1	ENST00000922942.1		c.31_42dupGGCGGCGGCGGC	p.Gly11_Gly14dup	conservative_inframe_insertion	Exon 1 of 12	ENSP00000593001.1
	TCF7L1	ENST00000868102.1		c.31_42dupGGCGGCGGCGGC	p.Gly11_Gly14dup	conservative_inframe_insertion	Exon 1 of 12	ENSP00000538161.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000322 AC: 3 AN: 930944 Hom.: 0 Cov.: 0 AF XY: 0.00000457 AC XY: 2 AN XY: 437378

African (AFR) AF: 0.00 AC: 0 AN: 18368

American (AMR) AF: 0.00 AC: 0 AN: 3854

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8384

East Asian (EAS) AF: 0.00 AC: 0 AN: 11214

South Asian (SAS) AF: 0.00 AC: 0 AN: 18060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11700

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2152

European-Non Finnish (NFE) AF: 0.00000364 AC: 3 AN: 823756

Other (OTH) AF: 0.00 AC: 0 AN: 33456

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 542

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.088

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs566806913; hg19: chr2-85360828;