NM_001367943.1:c.381+309dupT

Variant names:

• chr10-112951913-C-CT
• rs112385175
• NM_001367943.1:c.381+309dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001367943.1(TCF7L2):​c.381+309dupT 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
• Publications: 1 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: G2P, PanelApp Australia
• intellectual disability

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

  Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

LOC124902502 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.381+309dupT		intron	N/A	NP_001354872.1	Q9NQB0-1
	TCF7L2	NM_001146274.2		c.381+309dupT		intron	N/A	NP_001139746.1	Q9NQB0-7
	TCF7L2	NM_030756.5		c.381+309dupT		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.381+306_381+307insT		intron	N/A	ENSP00000348274.4	Q9NQB0-1
	TCF7L2	ENST00000627217.3	TSL:1	c.381+306_381+307insT		intron	N/A	ENSP00000486891.1	Q9NQB0-7
	TCF7L2	ENST00000369397.8	TSL:1	c.381+306_381+307insT		intron	N/A	ENSP00000358404.4	Q9NQB0-8

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

African (AFR) AF: 0.571 AC: 16 AN: 28

American (AMR) AF: 0.357 AC: 10 AN: 28

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 4 AN: 6

East Asian (EAS) AF: 0.0962 AC: 5 AN: 52

South Asian (SAS) AF: 0.00 AC: 0 AN: 10

European-Finnish (FIN) AF: 0.346 AC: 18 AN: 52

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.413 AC: 210 AN: 508

Other (OTH) AF: 0.553 AC: 21 AN: 38

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

African (AFR) AF: 0.644 AC: 26304 AN: 40816

American (AMR) AF: 0.592 AC: 8990 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1924 AN: 3452

East Asian (EAS) AF: 0.384 AC: 1931 AN: 5028

South Asian (SAS) AF: 0.496 AC: 2363 AN: 4766

European-Finnish (FIN) AF: 0.454 AC: 4679 AN: 10298

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36386 AN: 67590

Other (OTH) AF: 0.577 AC: 1211 AN: 2100

Alfa AF: 0.526 Hom.: 2071

Asia WGS AF: 0.432 AC: 1498 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs112385175; hg19: chr10-114711672;