Variant 7-87907283-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006716.4(DBF4):c.1145A>G(p.Gln382Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,614,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

DBF4
NM_006716.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.44

Variant links:

Genes affected

DBF4 (HGNC:17364): (DBF4-CDC7 kinase regulatory subunit) Predicted to enable protein serine/threonine kinase activator activity. Predicted to be involved in positive regulation of nuclear cell cycle DNA replication and regulation of cell cycle phase transition. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

DBF4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08961004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DBF4	NM_006716.4 linkuse as main transcript	c.1145A>G	p.Gln382Arg	missense_variant	12/12	ENST00000265728.6	NP_006707.1	Q9UBU7-1
DBF4	NM_001318061.2 linkuse as main transcript	c.473A>G	p.Gln158Arg	missense_variant	12/12		NP_001304990.1	Q9UBU7B7Z8C6
DBF4	NM_001318060.2 linkuse as main transcript	c.446A>G	p.Gln149Arg	missense_variant	11/11		NP_001304989.1	Q9UBU7B4DXK0
DBF4	NM_001318062.2 linkuse as main transcript	c.365A>G	p.Gln122Arg	missense_variant	12/12		NP_001304991.1	Q9UBU7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DBF4	ENST00000265728.6 linkuse as main transcript	c.1145A>G	p.Gln382Arg	missense_variant	12/12	1	NM_006716.4	ENSP00000265728.1		Q9UBU7-1

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251032

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.000432

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000821

AC:

AN:

1461698

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000919

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 03, 2024

The c.1145A>G (p.Q382R) alteration is located in exon 12 (coding exon 12) of the DBF4 gene. This alteration results from a A to G substitution at nucleotide position 1145, causing the glutamine (Q) at amino acid position 382 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.045

Eigen

Benign

-0.034

Eigen_PC

Benign

-0.052

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.71

M_CAP

Benign

0.017

MetaRNN

Benign

0.090

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.81

REVEL

Benign

0.090

Sift

Benign

0.43

Sift4G

Benign

0.79

Polyphen

0.99

Vest4

0.15

MVP

0.63

MPC

0.64

ClinPred

0.13

GERP RS

3.1

Varity_R

0.048

gMVP

0.12

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