Genetic Variant DBX2:p.Arg267Arg (chr12-45016505-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

3 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004329.3. 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
	DBX2	NM_001004329.3	MANE Select	c.801G>A	p.Arg267Arg	synonymous	Exon 4 of 4	NP_001004329.2	Q6ZNG2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DBX2	ENST00000332700.6	TSL:2 MANE Select	c.801G>A	p.Arg267Arg	synonymous	Exon 4 of 4	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

GnomAD2 exomes

AF:

0.00628

AC:

1572

AN:

250196

AF XY:

0.00577

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 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

African (AFR)

AF:

0.000449

AC:

AN:

33432

American (AMR)

AF:

0.000807

AC:

AN:

44588

Ashkenazi Jewish (ASJ)

AF:

0.000882

AC:

AN:

26076

East Asian (EAS)

AF:

0.0340

AC:

1347

AN:

39662

South Asian (SAS)

AF:

0.00186

AC:

160

AN:

86082

European-Finnish (FIN)

AF:

0.00255

AC:

136

AN:

53388

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00458

AC:

5087

AN:

1111700

Other (OTH)

AF:

0.00454

AC:

274

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

417

835

1252

1670

2087

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

212

424

636

848

1060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00381

AC:

580

AN:

152266

Hom.:

Cov.:

AF XY:

0.00372

AC XY:

277

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.000722

AC:

AN:

41558

American (AMR)

AF:

0.00111

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0438

AC:

227

AN:

5180

South Asian (SAS)

AF:

0.00166

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00179

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00407

AC:

277

AN:

68018

Other (OTH)

AF:

0.000949

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

118

148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00417

Hom.:

Bravo

AF:

0.00444

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.00393

EpiControl

AF:

0.00409

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.4

(source)

DANN

Benign

0.57

PhyloP100

-0.77

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over