10-113155455-G-C

Variant names:

• chr10-113155455-G-C
• rs290483
• NM_001367943.1:c.1270-2566G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001367943.1(TCF7L2):​c.1270-2566G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.823
• Publications: 15 publications found

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]

TCF7L2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P
• intellectual disability

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• congenital glaucoma

  Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367943.1. 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
	TCF7L2	NM_001367943.1	MANE Select	c.1270-2566G>C		intron	N/A	NP_001354872.1	Q9NQB0-1
	TCF7L2	NM_001146274.2		c.1270-2566G>C		intron	N/A	NP_001139746.1	Q9NQB0-7
	TCF7L2	NM_030756.5		c.1201-2566G>C		intron	N/A	NP_110383.2	Q9NQB0-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF7L2	ENST00000355995.9	TSL:1 MANE Select	c.1270-2566G>C		intron	N/A	ENSP00000348274.4	Q9NQB0-1
	TCF7L2	ENST00000627217.3	TSL:1	c.1270-2566G>C		intron	N/A	ENSP00000486891.1	Q9NQB0-7
	TCF7L2	ENST00000369397.8	TSL:1	c.1201-2566G>C		intron	N/A	ENSP00000358404.4	Q9NQB0-8

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151880 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 151880 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74160

African (AFR) AF: 0.00 AC: 0 AN: 41316

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2088

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.33
DANN	Benign	0.36
PhyloP100		-0.82

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

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

Other links and lift over

dbSNP: rs290483;

hg19: chr10-114915214;