Genetic Variant DBX2:p.Ala104Gly (chr12-45050617-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001004329.3(DBX2):c.311C>G(p.Ala104Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000358 in 1,398,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A104V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

DBX2
NM_001004329.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.83

Publications

2 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:

DBX2-AS1 (HGNC:55479): (DBX2 antisense RNA 1)

DBX2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40161178).

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.311C>G	p.Ala104Gly	missense	Exon 1 of 4	NP_001004329.2	Q6ZNG2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DBX2	ENST00000332700.6	TSL:2 MANE Select	c.311C>G	p.Ala104Gly	missense	Exon 1 of 4	ENSP00000331470.6	Q6ZNG2
DBX2-AS1	ENST00000829188.1		n.140+73G>C		intron	N/A
DBX2-AS1	ENST00000829190.1		n.180+73G>C		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000135

AC:

AN:

148082

AF XY:

0.0000126

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000809

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000358

AC:

AN:

1398170

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

689732

show subpopulations

African (AFR)

AF:

0.0000318

AC:

AN:

31488

American (AMR)

AF:

0.0000838

AC:

AN:

35798

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25134

East Asian (EAS)

AF:

0.00

AC:

AN:

35780

South Asian (SAS)

AF:

0.00

AC:

AN:

79274

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47992

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5490

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1079232

Other (OTH)

AF:

0.00

AC:

AN:

57982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

Eigen

Benign

0.029

Eigen_PC

Benign

-0.022

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.62

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.40

MetaSVM

Uncertain

-0.22

MutationAssessor

Uncertain

2.0

PhyloP100

1.8

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

0.22

REVEL

Uncertain

0.33

Sift

Benign

0.55

Sift4G

Benign

0.66

Polyphen

0.99

Vest4

0.29

MutPred

0.43

Loss of stability (P = 0.0733)

MVP

0.67

MPC

0.35

ClinPred

0.71

GERP RS

2.2

PromoterAI

0.052

Neutral

(source)

Varity_R

0.10

gMVP

0.39

Mutation Taster

=94/6

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over