Genetic Variant CDCA5:p.Glu123Lys (chr11-65079664-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.367G>A(p.Glu123Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,602,752 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 13 hom., cov: 32)

Exomes 𝑓: 0.00088 ( 14 hom. )

Consequence

CDCA5
NM_080668.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.284

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034635663).

BP6

Variant 11-65079664-C-T is Benign according to our data. Variant chr11-65079664-C-T is described in ClinVar as [Benign]. Clinvar id is 720322.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 = 0.00771 (1173/152172) while in subpopulation AFR AF= 0.0261 (1082/41520). AF 95% confidence interval is 0.0248. There are 13 homozygotes in gnomad4. There are 549 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDCA5	NM_080668.4 link	c.367G>A	p.Glu123Lys	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.367G>A	p.Glu123Lys	missense_variant	Exon 5 of 6	1	NM_080668.4	ENSP00000275517.3		Q96FF9

Frequencies

GnomAD3 genomes

AF:

0.00772

AC:

1174

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0262

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00354

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00767

GnomAD3 exomes

AF:

0.00200

AC:

470

AN:

235204

Hom.:

AF XY:

0.00152

AC XY:

194

AN XY:

127814

show subpopulations

Gnomad AFR exome

AF:

0.0270

Gnomad AMR exome

AF:

0.00122

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:

0.000190

Gnomad OTH exome

AF:

0.00120

GnomAD4 exome

AF:

0.000878

AC:

1274

AN:

1450580

Hom.:

Cov.:

AF XY:

0.000776

AC XY:

559

AN XY:

720466

show subpopulations

Gnomad4 AFR exome

AF:

0.0277

Gnomad4 AMR exome

AF:

0.00171

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000470

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000120

Gnomad4 OTH exome

AF:

0.00202

GnomAD4 genome

AF:

0.00771

AC:

1173

AN:

152172

Hom.:

Cov.:

AF XY:

0.00738

AC XY:

549

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0261

Gnomad4 AMR

AF:

0.00354

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00759

Alfa

AF:

0.00131

Hom.:

Bravo

AF:

0.00838

ESP6500AA

AF:

0.0246

AC:

108

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00219

AC:

266

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.0

DANN

Benign

0.56

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.49

T;T

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.019

Sift

Benign

0.36

T;T

Sift4G

Benign

0.30

T;T

Polyphen

0.11

B;.

Vest4

0.13

MVP

0.27

MPC

0.53

ClinPred

0.0080

GERP RS

-3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.048

gMVP

0.11

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