Variant 1-91508273-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003503.4(CDC7):c.211T>A(p.Ser71Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000125 in 1,597,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S71C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

CDC7
NM_003503.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.58

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:

CDC7 (HGNC:):

CDC7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28892565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC7	NM_003503.4 linkuse as main transcript	c.211T>A	p.Ser71Thr	missense_variant	4/12	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.211T>A	p.Ser71Thr	missense_variant	4/12	1	NM_003503.4	ENSP00000234626.6	O00311-1
CDC7	ENST00000428239.5 linkuse as main transcript	c.211T>A	p.Ser71Thr	missense_variant	4/12	1		ENSP00000393139.1	O00311-1
CDC7	ENST00000426137.1 linkuse as main transcript	c.211T>A	p.Ser71Thr	missense_variant	4/6	5		ENSP00000398077.1	B1AMW7
CDC7	ENST00000497611.1 linkuse as main transcript	n.597T>A		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000421

AC:

AN:

237794

Hom.:

AF XY:

0.0000155

AC XY:

AN XY:

128886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000336

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000104

AC:

AN:

1445172

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

718618

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000351

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000151

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

Jan 04, 2022

The c.211T>A (p.S71T) alteration is located in exon 4 (coding exon 3) of the CDC7 gene. This alteration results from a T to A substitution at nucleotide position 211, causing the serine (S) at amino acid position 71 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

0.22

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.090

T;T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

0.0091

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.81

.;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.58

N;N;.

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.11

Sift

Uncertain

0.021

D;D;T

Sift4G

Benign

0.35

T;T;D

Polyphen

0.050

B;B;.

Vest4

0.27

MutPred

0.55

Loss of disorder (P = 0.2213);Loss of disorder (P = 0.2213);Loss of disorder (P = 0.2213);

MVP

0.75

MPC

0.27

ClinPred

0.14

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.52

gMVP

0.63

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