Variant 3-141978663-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001178139.2(TFDP2):c.376G>A(p.Asp126Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,608,396 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: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

TFDP2
NM_001178139.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.74

Variant links:

Genes affected

TFDP2 (HGNC:11751): (transcription factor Dp-2) The gene is a member of the transcription factor DP family. The encoded protein forms heterodimers with the E2F transcription factors resulting in transcriptional activation of cell cycle regulated genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

TFDP2 links:

TFDP2 (HGNC:):

TFDP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27505124).

BS2

High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFDP2	NM_001178139.2 linkuse as main transcript	c.376G>A	p.Asp126Asn	missense_variant	7/13	ENST00000489671.6	NP_001171610.1	Q14188-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFDP2	ENST00000489671.6 linkuse as main transcript	c.376G>A	p.Asp126Asn	missense_variant	7/13	1	NM_001178139.2	ENSP00000420616.1		Q14188-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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

GnomAD3 exomes

AF:

0.0000247

AC:

AN:

242950

Hom.:

AF XY:

0.00000758

AC XY:

AN XY:

131884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000123

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1456280

Hom.:

Cov.:

AF XY:

0.00000966

AC XY:

AN XY:

724266

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000116

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.00000828

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000597

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 19, 2022

The c.376G>A (p.D126N) alteration is located in exon 7 (coding exon 6) of the TFDP2 gene. This alteration results from a G to A substitution at nucleotide position 376, causing the aspartic acid (D) at amino acid position 126 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.49

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

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

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.98

D;D;.;D;D;D;D;D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.28

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

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

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

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-3.2

D;.;D;D;D;D;D;D;D;D

REVEL

Benign

0.095

Sift

Uncertain

0.0070

D;.;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.011

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

Polyphen

0.0070

B;.;B;.;B;.;.;.;.;.

Vest4

0.22

MutPred

0.26

Gain of methylation at K127 (P = 0.0699);.;.;.;.;.;.;.;.;.;

MVP

0.068

MPC

0.28

ClinPred

0.44

GERP RS

5.3

Varity_R

0.30

gMVP

0.31

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

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