Variant 10-112951217-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001367943.1(TCF7L2):c.200G>A(p.Arg67Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000209 in 1,433,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 28)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TCF7L2
NM_001367943.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.98

Variant links:

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 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32472366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7L2	NM_001367943.1 linkuse as main transcript	c.200G>A	p.Arg67Gln	missense_variant	2/15	ENST00000355995.9	NP_001354872.1
LOC124902502	XR_007062291.1 linkuse as main transcript	n.566-210C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF7L2	ENST00000355995.9 linkuse as main transcript	c.200G>A	p.Arg67Gln	missense_variant	2/15	1	NM_001367943.1	ENSP00000348274		Q9NQB0-1
	ENST00000369391.3 linkuse as main transcript	n.99-210C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000209

AC:

AN:

1433798

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

712798

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000182

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.000230

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2023

TCF7L2: PM2, PP3 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

T;T;T;.;T;.;.;.;.;T;.;T;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.64

LIST_S2

Pathogenic

0.97

D;D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Pathogenic

0.97

MetaRNN

Benign

0.32

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Pathogenic

0.92

MutationAssessor

Benign

1.2

.;.;L;L;.;L;L;L;L;.;.;.;.

MutationTaster

Benign

0.98

D;D;D;D;D;D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.1

N;N;N;N;N;.;N;N;N;N;N;.;N

REVEL

Uncertain

0.50

Sift

Benign

0.17

T;T;T;T;T;.;T;T;T;T;T;.;D

Sift4G

Benign

0.42

T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.49, 0.012, 0.028

.;P;.;.;.;B;.;.;.;.;B;.;.

Vest4

0.25

MVP

0.85

MPC

1.2

ClinPred

0.31

GERP RS

1.8

Varity_R

0.15

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over