Genetic Variant ZDBF2:p.Gln129Arg (chr2-206304914-A-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -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. 15/21 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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 735252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDBF2	NM_020923.3 link	c.386A>G	p.Gln129Arg	missense_variant	Exon 5 of 5	ENST00000374423.9	NP_065974.1	Q9HCK1N0DVB2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDBF2	ENST00000374423.9 link	c.386A>G	p.Gln129Arg	missense_variant	Exon 5 of 5	1	NM_020923.3	ENSP00000363545.3		Q9HCK1

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

GnomAD3 exomes

AF:

0.00292

AC:

727

AN:

248664

Hom.:

AF XY:

0.00313

AC XY:

422

AN XY:

134904

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 SAS exome

AF:

0.00128

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

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.00249

Gnomad4 ASJ exome

AF:

0.00138

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00139

Gnomad4 FIN exome

AF:

0.000862

Gnomad4 NFE exome

AF:

0.00624

Gnomad4 OTH exome

AF:

0.00623

GnomAD4 genome

AF:

0.00347

AC:

529

AN:

152274

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

241

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.00425

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00596

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00447

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

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ZDBF2: BP4, BS2 -

Nov 18, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.2

DANN

Benign

0.96

DEOGEN2

Benign

0.0057

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

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.096

M_CAP

Benign

0.0046

MetaRNN

Benign

0.0060

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

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

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.3

N;.;.;.;.;.;.;.

REVEL

Benign

0.023

Sift

Benign

0.21

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

Sift4G

Benign

0.28

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

Polyphen

0.0010

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

Vest4

0.069

MVP

0.085

MPC

0.061

ClinPred

0.0041

GERP RS

1.0

Varity_R

0.022

gMVP

0.025

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