Genetic Variant CDCA5:p.Gly179Arg (chr11-65079496-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_080668.4(CDCA5):c.535G>A(p.Gly179Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,614,132 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 18 hom., cov: 32)

Exomes 𝑓: 0.00082 ( 19 hom. )

Consequence

CDCA5
NM_080668.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.629

Variant links:

Genes affected

CDCA5 (HGNC:14626): (cell division cycle associated 5) Predicted to enable chromatin binding activity. Involved in double-strand break repair; mitotic sister chromatid segregation; and regulation of cell cycle process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CDCA5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054317117).

BP6

Variant 11-65079496-C-T is Benign according to our data. Variant chr11-65079496-C-T is described in ClinVar as [Benign]. Clinvar id is 781003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00759 (1156/152238) while in subpopulation AFR AF= 0.0268 (1115/41532). AF 95% confidence interval is 0.0255. There are 18 homozygotes in gnomad4. There are 547 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDCA5	NM_080668.4 link	c.535G>A	p.Gly179Arg	missense_variant	Exon 5 of 6	ENST00000275517.8	NP_542399.1	Q96FF9A0A024R5D6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDCA5	ENST00000275517.8 link	c.535G>A	p.Gly179Arg	missense_variant	Exon 5 of 6	1	NM_080668.4	ENSP00000275517.3		Q96FF9

Frequencies

GnomAD3 genomes

AF:

0.00759

AC:

1155

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0269

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00206

AC:

518

AN:

251432

Hom.:

AF XY:

0.00154

AC XY:

209

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0287

Gnomad AMR exome

AF:

0.000809

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000822

AC:

1202

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000716

AC XY:

521

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0272

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000113

Gnomad4 OTH exome

AF:

0.00179

GnomAD4 genome

AF:

0.00759

AC:

1156

AN:

152238

Hom.:

Cov.:

AF XY:

0.00735

AC XY:

547

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0268

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00157

Hom.:

Bravo

AF:

0.00886

ESP6500AA

AF:

0.0241

AC:

106

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00252

AC:

306

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 17, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.67

CADD

Benign

5.1

DANN

Benign

0.81

DEOGEN2

Benign

0.058

T;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.65

T;T

MetaRNN

Benign

0.0054

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;.

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.1

D;D

REVEL

Benign

0.027

Sift

Benign

0.37

T;T

Sift4G

Benign

0.92

T;T

Polyphen

0.21

B;.

Vest4

0.20

MutPred

0.42

Gain of solvent accessibility (P = 0.0014);Gain of solvent accessibility (P = 0.0014);

MVP

0.45

MPC

0.54

ClinPred

0.010

GERP RS

-0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.050

gMVP

0.060

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