rs758866134

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_031942.5(CDCA7):c.146C>G(p.Thr49Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000411 in 1,459,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T49M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CDCA7
NM_031942.5 missense, splice_region

Scores

Splicing: ADA: 0.9926

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.12

Publications

0 publications found

Variant links:

Genes affected

CDCA7 (HGNC:14628): (cell division cycle associated 7) This gene was identified as a c-Myc responsive gene, and behaves as a direct c-Myc target gene. Overexpression of this gene is found to enhance the transformation of lymphoblastoid cells, and it complements a transformation-defective Myc Box II mutant, suggesting its involvement in c-Myc-mediated cell transformation. Two alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

CDCA7 Gene-Disease associations (from GenCC):

immunodeficiency-centromeric instability-facial anomalies syndrome 3
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
immunodeficiency-centromeric instability-facial anomalies syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CDCA7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031942.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDCA7	NM_031942.5	MANE Select	c.146C>G	p.Thr49Arg	missense splice_region	Exon 2 of 10	NP_114148.3
	CDCA7	NM_145810.3		c.146C>G	p.Thr49Arg	missense splice_region	Exon 2 of 9	NP_665809.1	Q9BWT1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDCA7	ENST00000306721.8	TSL:2 MANE Select	c.146C>G	p.Thr49Arg	missense splice_region	Exon 2 of 10	ENSP00000306968.3	Q9BWT1-2
CDCA7	ENST00000347703.7	TSL:1	c.146C>G	p.Thr49Arg	missense splice_region	Exon 2 of 9	ENSP00000272789.4	Q9BWT1-1
CDCA7	ENST00000467411.5	TSL:1	n.217C>G		splice_region non_coding_transcript_exon	Exon 2 of 7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000160

AC:

AN:

250218

AF XY:

0.0000148

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1459844

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

725956

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33424

American (AMR)

AF:

0.00

AC:

AN:

44496

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26074

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.00

AC:

AN:

85878

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1110832

Other (OTH)

AF:

0.00

AC:

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.61

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.56

M_CAP

Benign

0.032

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.9

PhyloP100

7.1

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.29

Sift

Uncertain

0.020

Sift4G

Benign

0.36

Polyphen

1.0

Vest4

0.51

MutPred

0.22

Gain of helix (P = 0.0128)

MVP

0.66

MPC

1.1

ClinPred

0.84

GERP RS

5.8

Varity_R

0.35

gMVP

0.41

Mutation Taster

=55/45

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.87

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over