Variant 1-91511851-G-A 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_003503.4(CDC7):c.500G>A(p.Arg167His) variant causes a missense change. The variant allele was found at a frequency of 0.0000117 in 1,452,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CDC7
NM_003503.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.08

Variant links:

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 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=0.20319626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC7	NM_003503.4 linkuse as main transcript	c.500G>A	p.Arg167His	missense_variant	6/12	ENST00000234626.11	NP_003494.1	O00311-1A0A384MTU6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CDC7	ENST00000234626.11 linkuse as main transcript	c.500G>A	p.Arg167His	missense_variant	6/12	1	NM_003503.4	ENSP00000234626.6	O00311-1
CDC7	ENST00000428239.5 linkuse as main transcript	c.500G>A	p.Arg167His	missense_variant	6/12	1		ENSP00000393139.1	O00311-1
CDC7	ENST00000426137.1 linkuse as main transcript	c.*28G>A		downstream_gene_variant		5		ENSP00000398077.1	B1AMW7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250396

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135384

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1452630

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

721512

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000585

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000109

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

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

Aug 31, 2022

The c.500G>A (p.R167H) alteration is located in exon 6 (coding exon 5) of the CDC7 gene. This alteration results from a G to A substitution at nucleotide position 500, causing the arginine (R) at amino acid position 167 to be replaced by a histidine (H). 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

0.11

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

T;T

Eigen

Benign

-0.15

Eigen_PC

Benign

0.076

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.90

.;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.45

N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.45

N;N

REVEL

Benign

0.24

Sift

Benign

0.22

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.39

B;B

Vest4

0.28

MutPred

0.61

Loss of MoRF binding (P = 0.007);Loss of MoRF binding (P = 0.007);

MVP

0.81

MPC

0.39

ClinPred

0.77

GERP RS

5.0

Varity_R

0.22

gMVP

0.54

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