11-65079496-C-T

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

1
17

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]

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=0.0054317117).
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
CDCA5NM_080668.4 linkc.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
CDCA5ENST00000275517.8 linkc.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.:
18
Cov.:
32
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.:
6
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.:
19
Cov.:
32
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.:
18
Cov.:
32
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.:
3
Bravo
AF:
0.00886
ESP6500AA
AF:
0.0241
AC:
106
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00252
AC:
306
Asia WGS
AF:
0.000866
AC:
3
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
T
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
N
LIST_S2
Benign
0.65
T;T
MetaRNN
Benign
0.0054
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.55
N;.
PrimateAI
Benign
0.26
T
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
T
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.

Other links and lift over

dbSNP: rs34032604; hg19: chr11-64846968; API