11-65079523-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080668.4(CDCA5):​c.508G>A​(p.Gly170Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CDCA5
NM_080668.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.06
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15506023).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDCA5NM_080668.4 linkc.508G>A p.Gly170Arg 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.508G>A p.Gly170Arg missense_variant Exon 5 of 6 1 NM_080668.4 ENSP00000275517.3 Q96FF9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 06, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.508G>A (p.G170R) alteration is located in exon 5 (coding exon 5) of the CDCA5 gene. This alteration results from a G to A substitution at nucleotide position 508, causing the glycine (G) at amino acid position 170 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
1.5
DANN
Benign
0.88
DEOGEN2
Benign
0.0097
T;T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.68
T;T
M_CAP
Benign
0.0055
T
MetaRNN
Benign
0.16
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.7
L;.
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-1.4
N;N
REVEL
Benign
0.090
Sift
Benign
0.17
T;T
Sift4G
Benign
0.89
T;T
Polyphen
0.0030
B;.
Vest4
0.15
MutPred
0.67
Gain of solvent accessibility (P = 0.0674);Gain of solvent accessibility (P = 0.0674);
MVP
0.30
MPC
0.56
ClinPred
0.18
T
GERP RS
-4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.098
gMVP
0.050

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-64846995; API