chr1-91511810-A-C

Position:

• chr1-91511810-A-C

Variant summary

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

The NM_003503.4(CDC7):​c.459A>C​(p.Glu153Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDC7 NM_003503.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.46

Genes affected

CDC7 (HGNC:1745): (cell division cycle 7) This gene encodes a cell division cycle protein with kinase activity that is critical for the G1/S transition. The yeast homolog is also essential for initiation of DNA replication as cell division occurs. Overexpression of this gene product may be associated with neoplastic transformation for some tumors. Multiple alternatively spliced transcript variants that encode the same protein have been detected. [provided by RefSeq, Aug 2008]

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	Protein	UniProt
CDC7	NM_003503.4	c.459A>C	p.Glu153Asp	missense_variant	6/12	ENST00000234626.11	NP_003494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC7	ENST00000234626.11	c.459A>C	p.Glu153Asp	missense_variant	6/12	1	NM_003503.4	ENSP00000234626.6
CDC7	ENST00000428239.5	c.459A>C	p.Glu153Asp	missense_variant	6/12	1		ENSP00000393139.1
CDC7	ENST00000426137.1	c.459A>C	p.Glu153Asp	missense_variant	6/6	5		ENSP00000398077.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Sep 29, 2022

The c.459A>C (p.E153D) alteration is located in exon 6 (coding exon 5) of the CDC7 gene. This alteration results from a A to C substitution at nucleotide position 459, causing the glutamic acid (E) at amino acid position 153 to be replaced by an aspartic acid (D). 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	0.44
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T;.
Eigen	Benign	-0.054
Eigen_PC	Benign	0.042
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.85	.;D;T
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.46	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.3	L;L;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.28
Sift	Benign	0.14	T;T;T
Sift4G	Benign	0.066	T;T;T
Polyphen		0.50	P;P;.
Vest4		0.41
MutPred		0.61		Gain of MoRF binding (P = 0.1801);Gain of MoRF binding (P = 0.1801);Gain of MoRF binding (P = 0.1801);
MVP		0.77
MPC		0.56
ClinPred		0.88	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.42
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr1-91977367;