10-112951913-C-CT

Position:

• chr10-112951913-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001367943.1(TCF7L2):​c.381+309dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.56 (23994 hom., cov: 0)
  • Exomes 𝑓: 0.39 (77 hom.)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.441

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]

LOC124902502 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 10-112951913-C-CT is Benign according to our data. Variant chr10-112951913-C-CT is described in ClinVar as [Benign]. Clinvar id is 1278027.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF7L2	NM_001367943.1	c.381+309dup		intron_variant		ENST00000355995.9	NP_001354872.1
LOC124902502	XR_007062291.1	n.429_430insA		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF7L2	ENST00000355995.9	c.381+309dup		intron_variant		1	NM_001367943.1	ENSP00000348274
	ENST00000369391.3			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.562 AC: 84426 AN: 150300 Hom.: 23967 Cov.: 0

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.580

GnomAD4 exome AF: 0.392 AC: 284 AN: 724 Hom.: 77 Cov.: 0 AF XY: 0.424 AC XY: 202 AN XY: 476

Gnomad4 AFR exome AF: 0.571

Gnomad4 AMR exome AF: 0.357

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.0962

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.413

Gnomad4 OTH exome AF: 0.553

GnomAD4 genome AF: 0.562 AC: 84501 AN: 150420 Hom.: 23994 Cov.: 0 AF XY: 0.556 AC XY: 40796 AN XY: 73428

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.577

Alfa AF: 0.526 Hom.: 2071

Asia WGS AF: 0.432 AC: 1498 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2019

- -

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: rs112385175; hg19: chr10-114711672;