Genetic Variant NM_080668.4:c.654G>A (chr11-65079377-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4BP6_ModerateBP7BS2

The NM_080668.4(CDCA5):c.654G>A(p.Lys218Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,614,106 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 8 hom. )

Consequence

CDCA5
NM_080668.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.959

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.271).

BP6

Variant 11-65079377-C-T is Benign according to our data. Variant chr11-65079377-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 709975.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.959 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 8 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080668.4. 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
	CDCA5	NM_080668.4	MANE Select	c.654G>A	p.Lys218Lys	synonymous	Exon 5 of 6	NP_542399.1	Q96FF9
	CDCA5	NM_001433518.1		c.654G>A	p.Lys218Lys	synonymous	Exon 5 of 10	NP_001420447.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDCA5	ENST00000275517.8	TSL:1 MANE Select	c.654G>A	p.Lys218Lys	synonymous	Exon 5 of 6	ENSP00000275517.3	Q96FF9
CDCA5	ENST00000479032.6	TSL:1	n.924G>A		non_coding_transcript_exon	Exon 4 of 5
CDCA5	ENST00000404147.3	TSL:2	c.654G>A	p.Lys218Lys	synonymous	Exon 5 of 5	ENSP00000385711.3	B5MBX0

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

209

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00260

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00122

AC:

308

AN:

251466

AF XY:

0.00119

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.00239

Gnomad OTH exome

AF:

0.000814

GnomAD4 exome

AF:

0.00286

AC:

4184

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00272

AC XY:

1978

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.000657

AC:

AN:

33480

American (AMR)

AF:

0.000291

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000337

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00364

AC:

4045

AN:

1112012

Other (OTH)

AF:

0.00142

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

239

478

718

957

1196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

336

504

672

840

<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

AF:

0.00137

AC:

209

AN:

152220

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.000626

AC:

AN:

41552

American (AMR)

AF:

0.000196

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00260

AC:

177

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00181

Hom.:

Bravo

AF:

0.00128

EpiCase

AF:

0.00142

EpiControl

AF:

0.00243

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

0.96

PromoterAI

-0.040

Neutral

(source)

Mutation Taster

=99/1

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over