1-91513197-C-G

Position:

• chr1-91513197-C-G

Variant summary

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

The NM_003503.4(CDC7):​c.712C>G​(p.Leu238Val) 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. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDC7 NM_003503.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.233

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]

CDC7 (HGNC:):

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.712C>G	p.Leu238Val	missense_variant	7/12	ENST00000234626.11	NP_003494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC7	ENST00000234626.11	c.712C>G	p.Leu238Val	missense_variant	7/12	1	NM_003503.4	ENSP00000234626.6
CDC7	ENST00000428239.5	c.712C>G	p.Leu238Val	missense_variant	7/12	1		ENSP00000393139.1
CDC7	ENST00000486509.1	n.71C>G		non_coding_transcript_exon_variant	1/4	3

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

Jul 11, 2023

The c.712C>G (p.L238V) alteration is located in exon 7 (coding exon 6) of the CDC7 gene. This alteration results from a C to G substitution at nucleotide position 712, causing the leucine (L) at amino acid position 238 to be replaced by a valine (V). 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	0.061
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.4
DANN	Benign	0.71
DEOGEN2	Benign	0.077	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.62	.;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.077	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.17	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.49	N;N
REVEL	Benign	0.019
Sift	Benign	0.62	T;T
Sift4G	Benign	0.56	T;T
Polyphen		0.0030	B;B
Vest4		0.088
MutPred		0.48		Loss of catalytic residue at L238 (P = 0.0233);Loss of catalytic residue at L238 (P = 0.0233);
MVP		0.59
MPC		0.17
ClinPred		0.025	T
GERP RS		-1.1
Varity_R		0.030
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.40		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.40		Position offset: -1

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: chr1-91978754;