2-85133705-GGGC-G

Position:

• chr2-85133705-GGGC-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000282111.4(TCF7L1):​c.40_42del​(p.Gly14del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 1,073,848 control chromosomes in the GnomAD database, including 92,149 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.44 (14475 hom., cov: 0)
  • Exomes 𝑓: 0.41 (77674 hom.)
• Consequence: TCF7L1 ENST00000282111.4 inframe_deletion
• Clinical Significance: Likely benign no assertion criteria provided B:2
• 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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7L1	NM_031283.3	c.40_42del	p.Gly14del	inframe_deletion	1/12	ENST00000282111.4	NP_112573.1
TCF7L1	XM_006712109.3	c.40_42del	p.Gly14del	inframe_deletion	1/12		XP_006712172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF7L1	ENST00000282111.4	c.40_42del	p.Gly14del	inframe_deletion	1/12	1	NM_031283.3	ENSP00000282111	P1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 63569 AN: 145690 Hom.: 14441 Cov.: 0

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.390

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.400

GnomAD3 exomes AF: 0.454 AC: 236 AN: 520 Hom.: 56 AF XY: 0.423 AC XY: 127 AN XY: 300

Gnomad AFR exome AF: 1.00

Gnomad AMR exome AF: 1.00

Gnomad FIN exome AF: 0.533

Gnomad NFE exome AF: 0.445

Gnomad OTH exome AF: 0.300

GnomAD4 exome AF: 0.412 AC: 382737 AN: 928050 Hom.: 77674 AF XY: 0.411 AC XY: 179196 AN XY: 435986

Gnomad4 AFR exome AF: 0.557

Gnomad4 AMR exome AF: 0.415

Gnomad4 ASJ exome AF: 0.412

Gnomad4 EAS exome AF: 0.269

Gnomad4 SAS exome AF: 0.327

Gnomad4 FIN exome AF: 0.581

Gnomad4 NFE exome AF: 0.412

Gnomad4 OTH exome AF: 0.396

GnomAD4 genome AF: 0.437 AC: 63645 AN: 145798 Hom.: 14475 Cov.: 0 AF XY: 0.437 AC XY: 30962 AN XY: 70914

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.398

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

Submissions by phenotype

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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;