10-112951893-A-AG

Position:

• chr10-112951893-A-AG

Variant summary

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

The NM_001367943.1(TCF7L2):​c.381+294dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (3515 hom., cov: 20)
  • Exomes 𝑓: 0.14 (17 hom.)
• Consequence: TCF7L2 NM_001367943.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.508

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 10-112951893-A-AG is Benign according to our data. Variant chr10-112951893-A-AG is described in ClinVar as [Benign]. Clinvar id is 1239575.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF7L2	NM_001367943.1	c.381+294dup		intron_variant		ENST00000355995.9
LOC124902502	XR_007062291.1	n.449_450insC		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF7L2	ENST00000355995.9	c.381+294dup		intron_variant		1	NM_001367943.1
	ENST00000369391.3			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.217 AC: 30648 AN: 141354 Hom.: 3510 Cov.: 20

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0676

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.138 AC: 185 AN: 1342 Hom.: 17 Cov.: 0 AF XY: 0.149 AC XY: 125 AN XY: 840

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.157

GnomAD4 genome AF: 0.217 AC: 30666 AN: 141452 Hom.: 3515 Cov.: 20 AF XY: 0.215 AC XY: 14817 AN XY: 68888

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.0680

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.226

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

Aug 15, 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: rs55688545; hg19: chr10-114711652;