11-65079477-C-G

Variant names:

• chr11-65079477-C-G
• NM_080668.4:c.554G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080668.4(CDCA5):​c.554G>C​(p.Cys185Ser) 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. 16/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.31
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05353877).

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.554G>C	p.Cys185Ser	missense	Exon 5 of 6	NP_542399.1	Q96FF9
	CDCA5	NM_001433518.1		c.554G>C	p.Cys185Ser	missense	Exon 5 of 10	NP_001420447.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDCA5	ENST00000275517.8	TSL:1 MANE Select	c.554G>C	p.Cys185Ser	missense	Exon 5 of 6	ENSP00000275517.3	Q96FF9
	CDCA5	ENST00000479032.6	TSL:1	n.824G>C		non_coding_transcript_exon	Exon 4 of 5
	CDCA5	ENST00000404147.3	TSL:2	c.554G>C	p.Cys185Ser	missense	Exon 5 of 5	ENSP00000385711.3	B5MBX0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.10
DANN	Benign	0.59
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-1.3
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.029
Sift	Benign	0.92	T
Sift4G	Benign	0.41	T
Polyphen		0.0030	B
Vest4		0.082
MutPred		0.51		Gain of disorder (P = 0.0295)
MVP		0.13
MPC		0.56
ClinPred		0.035	T
GERP RS		-5.8
PromoterAI		0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.030
gMVP		0.042
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

hg19: chr11-64846949;