Genetic Variant ZDBF2:p.Asp99Val (chr2-206304824-A-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_020923.3(ZDBF2):c.296A>T(p.Asp99Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,613,726 control chromosomes in the GnomAD database, including 10 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 Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 10 hom. )

Consequence

ZDBF2
NM_020923.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.250

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005754411).

BP6

Variant 2-206304824-A-T is Benign according to our data. Variant chr2-206304824-A-T is described in ClinVar as [Benign]. Clinvar id is 2823821.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDBF2	NM_020923.3 link	c.296A>T	p.Asp99Val	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.296A>T	p.Asp99Val	missense_variant	Exon 5 of 5	1	NM_020923.3	ENSP00000363545.3		Q9HCK1

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

161

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00519

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00125

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00175

AC:

435

AN:

249022

Hom.:

AF XY:

0.00208

AC XY:

281

AN XY:

135086

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.00102

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00690

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00156

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00132

AC:

1932

AN:

1461534

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

1106

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00748

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000971

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.00106

AC:

161

AN:

152192

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00519

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00125

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00157

Hom.:

Bravo

AF:

0.00106

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00132

AC:

ExAC

AF:

0.00182

AC:

220

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00289

EpiControl

AF:

0.00243

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

5.1

DANN

Benign

0.76

DEOGEN2

Benign

0.017

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

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.37

M_CAP

Benign

0.0015

MetaRNN

Benign

0.0058

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

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

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.6

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

REVEL

Benign

0.059

Sift

Benign

0.085

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

Sift4G

Uncertain

0.033

D;.;.;.;.;.;.;D

Polyphen

0.65

P;P;.;.;.;.;.;.

Vest4

0.21

MVP

0.21

MPC

0.34

ClinPred

0.035

GERP RS

1.5

Varity_R

0.11

gMVP

0.040

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