7-87907694-A-C

Position:

• chr7-87907694-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006716.4(DBF4):​c.1556A>C​(p.Lys519Thr) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DBF4 NM_006716.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.77

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15527835).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DBF4	NM_006716.4	c.1556A>C	p.Lys519Thr	missense_variant	12/12	ENST00000265728.6
DBF4	NM_001318061.2	c.884A>C	p.Lys295Thr	missense_variant	12/12
DBF4	NM_001318060.2	c.857A>C	p.Lys286Thr	missense_variant	11/11
DBF4	NM_001318062.2	c.776A>C	p.Lys259Thr	missense_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DBF4	ENST00000265728.6	c.1556A>C	p.Lys519Thr	missense_variant	12/12	1	NM_006716.4	P1
DBF4	ENST00000413643.5	c.*790A>C		3_prime_UTR_variant, NMD_transcript_variant	12/12	1
DBF4	ENST00000431138.5	c.*1329A>C		3_prime_UTR_variant, NMD_transcript_variant	12/12	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Aug 17, 2022

The c.1556A>C (p.K519T) alteration is located in exon 12 (coding exon 12) of the DBF4 gene. This alteration results from a A to C substitution at nucleotide position 1556, causing the lysine (K) at amino acid position 519 to be replaced by a threonine (T). 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	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.042
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	0.95	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.092
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.024	D
Polyphen		0.75	P
Vest4		0.18
MutPred		0.22		Loss of ubiquitination at K519 (P = 0.0233);
MVP		0.12
MPC		0.33
ClinPred		0.54	D
GERP RS		4.0
Varity_R		0.091
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-87537009;