Genetic Variant NM_020923.3:c.386A>G (chr2-206304914-A-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_020923.3(ZDBF2):c.386A>G(p.Gln129Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00508 in 1,613,716 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 34 hom. )

Consequence

ZDBF2
NM_020923.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.43

Publications

2 publications found

Variant links:

Genes affected

ZDBF2 (HGNC:29313): (zinc finger DBF-type containing 2) This gene encodes a protein containing DBF4-type zinc finger domains. This gene is imprinted and paternally expressed in lymphocytes but is more stochastically expressed in the placenta. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

ZDBF2 Gene-Disease associations (from GenCC):

nasopalpebral lipoma-coloboma syndrome
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ZDBF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059749186).

BP6

Variant 2-206304914-A-G is Benign according to our data. Variant chr2-206304914-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 735252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 529 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020923.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZDBF2	NM_020923.3	MANE Select	c.386A>G	p.Gln129Arg	missense	Exon 5 of 5	NP_065974.1	Q9HCK1
ZDBF2	NM_001369654.1		c.386A>G	p.Gln129Arg	missense	Exon 6 of 6	NP_001356583.1	N0DVB2
ZDBF2	NM_001285549.2		c.380A>G	p.Gln127Arg	missense	Exon 7 of 7	NP_001272478.1	N0DVX5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZDBF2	ENST00000374423.9	TSL:1 MANE Select	c.386A>G	p.Gln129Arg	missense	Exon 5 of 5	ENSP00000363545.3	Q9HCK1
ZDBF2	ENST00000649650.1		c.386A>G	p.Gln129Arg	missense	Exon 6 of 6	ENSP00000497308.1	Q9HCK1
ZDBF2	ENST00000920103.1		c.386A>G	p.Gln129Arg	missense	Exon 6 of 6	ENSP00000590162.1

Frequencies

GnomAD3 genomes

AF:

0.00348

AC:

529

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00426

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00596

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00292

AC:

727

AN:

248664

AF XY:

0.00313

show subpopulations

Gnomad AFR exome

AF:

0.000969

Gnomad AMR exome

AF:

0.00239

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.0000557

Gnomad FIN exome

AF:

0.000837

Gnomad NFE exome

AF:

0.00474

Gnomad OTH exome

AF:

0.00432

GnomAD4 exome

AF:

0.00524

AC:

7663

AN:

1461442

Hom.:

Cov.:

AF XY:

0.00513

AC XY:

3728

AN XY:

727004

show subpopulations

African (AFR)

AF:

0.000807

AC:

AN:

33468

American (AMR)

AF:

0.00249

AC:

111

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.00138

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39692

South Asian (SAS)

AF:

0.00139

AC:

120

AN:

86238

European-Finnish (FIN)

AF:

0.000862

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00624

AC:

6941

AN:

1111752

Other (OTH)

AF:

0.00623

AC:

376

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

492

983

1475

1966

2458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

282

564

846

1128

1410

<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:

0.00347

AC:

529

AN:

152274

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

241

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.000962

AC:

AN:

41586

American (AMR)

AF:

0.00425

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00166

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00596

AC:

405

AN:

68000

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

107

134

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:

0.00421

Hom.:

Bravo

AF:

0.00369

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00210

AC:

ESP6500EA

AF:

0.00545

AC:

ExAC

AF:

0.00285

AC:

345

EpiCase

AF:

0.00605

EpiControl

AF:

0.00499

ClinVar

ClinVar submissions

Significance:Likely 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

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.2

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0057

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.096

M_CAP

Benign

0.0046

MetaRNN

Benign

0.0060

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

1.4

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.3

REVEL

Benign

0.023

Sift

Benign

0.21

Sift4G

Benign

0.28

Polyphen

0.0010

Vest4

0.069

MVP

0.085

MPC

0.061

ClinPred

0.0041

GERP RS

1.0

Varity_R

0.022

gMVP

0.025

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