7-87900302-T-G

Position:

• chr7-87900302-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006716.4(DBF4):​c.762T>G​(p.Asp254Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DBF4 NM_006716.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.987

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DBF4	NM_006716.4	c.762T>G	p.Asp254Glu	missense_variant	9/12	ENST00000265728.6
DBF4	NM_001318061.2	c.90T>G	p.Asp30Glu	missense_variant	9/12
DBF4	NM_001318060.2	c.63T>G	p.Asp21Glu	missense_variant	8/11
DBF4	NM_001318062.2	c.-19T>G		5_prime_UTR_variant	9/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DBF4	ENST00000265728.6	c.762T>G	p.Asp254Glu	missense_variant	9/12	1	NM_006716.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2021

The c.762T>G (p.D254E) alteration is located in exon 9 (coding exon 9) of the DBF4 gene. This alteration results from a T to G substitution at nucleotide position 762, causing the aspartic acid (D) at amino acid position 254 to be replaced by a glutamic acid (E). 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	Uncertain	0.36
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.087
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	0.96	N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.050
Sift	Benign	0.78	T
Sift4G	Benign	0.51	T
Polyphen		0.82	P
Vest4		0.30
MutPred		0.29		Gain of methylation at K257 (P = 0.0904);
MVP		0.30
MPC		0.62
ClinPred		0.78	D
GERP RS		3.1
Varity_R		0.15
gMVP		0.098

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.27		Position offset: 47

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-87529617;