Variant 12-45016505-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001004329.3(DBX2):c.801G>A(p.Arg267Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00475 in 1,613,300 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 43 hom. )

Consequence

DBX2
NM_001004329.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.773

Variant links:

Genes affected

DBX2 (HGNC:33186): (developing brain homeobox 2) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

DBX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 12-45016505-C-T is Benign according to our data. Variant chr12-45016505-C-T is described in ClinVar as [Benign]. Clinvar id is 710738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.773 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00381 (580/152266) while in subpopulation EAS AF= 0.0438 (227/5180). AF 95% confidence interval is 0.0392. There are 7 homozygotes in gnomad4. There are 277 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBX2	NM_001004329.3 linkuse as main transcript	c.801G>A	p.Arg267Arg	synonymous_variant	4/4	ENST00000332700.6	NP_001004329.2	Q6ZNG2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DBX2	ENST00000332700.6 linkuse as main transcript	c.801G>A	p.Arg267Arg	synonymous_variant	4/4	2	NM_001004329.3	ENSP00000331470.6		Q6ZNG2

Frequencies

GnomAD3 genomes

AF:

0.00381

AC:

580

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0437

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00407

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.00628

AC:

1572

AN:

250196

Hom.:

AF XY:

0.00577

AC XY:

780

AN XY:

135236

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.000641

Gnomad ASJ exome

AF:

0.000800

Gnomad EAS exome

AF:

0.0462

Gnomad SAS exome

AF:

0.00131

Gnomad FIN exome

AF:

0.00204

Gnomad NFE exome

AF:

0.00507

Gnomad OTH exome

AF:

0.00461

GnomAD4 exome

AF:

0.00485

AC:

7087

AN:

1461034

Hom.:

Cov.:

AF XY:

0.00473

AC XY:

3439

AN XY:

726818

show subpopulations

Gnomad4 AFR exome

AF:

0.000449

Gnomad4 AMR exome

AF:

0.000807

Gnomad4 ASJ exome

AF:

0.000882

Gnomad4 EAS exome

AF:

0.0340

Gnomad4 SAS exome

AF:

0.00186

Gnomad4 FIN exome

AF:

0.00255

Gnomad4 NFE exome

AF:

0.00458

Gnomad4 OTH exome

AF:

0.00454

GnomAD4 genome

AF:

0.00381

AC:

580

AN:

152266

Hom.:

Cov.:

AF XY:

0.00372

AC XY:

277

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0438

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00407

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.00406

Hom.:

Bravo

AF:

0.00444

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.00393

EpiControl

AF:

0.00409

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.4

DANN

Benign

0.57

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