1-37692917-T-C

Position:

• chr1-37692917-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001256875.2(CDCA8):​c.107T>C​(p.Ile36Thr) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CDCA8 NM_001256875.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0990

Genes affected

CDCA8 (HGNC:14629): (cell division cycle associated 8) This gene encodes a component of the chromosomal passenger complex. This complex is an essential regulator of mitosis and cell division. This protein is cell-cycle regulated and is required for chromatin-induced microtubule stabilization and spindle formation. Alternate splicing results in multiple transcript variants. Pseudgenes of this gene are found on chromosomes 7, 8 and 16. [provided by RefSeq, Apr 2013]

ACMG classification

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=0.06949523).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDCA8	NM_001256875.2	c.107T>C	p.Ile36Thr	missense_variant	2/10	ENST00000373055.6
CDCA8	NM_018101.4	c.107T>C	p.Ile36Thr	missense_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDCA8	ENST00000373055.6	c.107T>C	p.Ile36Thr	missense_variant	2/10	1	NM_001256875.2	P1
CDCA8	ENST00000327331.2	c.107T>C	p.Ile36Thr	missense_variant	3/11	1		P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 11, 2023

The c.107T>C (p.I36T) alteration is located in exon 3 (coding exon 2) of the CDCA8 gene. This alteration results from a T to C substitution at nucleotide position 107, causing the isoleucine (I) at amino acid position 36 to be replaced by a threonine (T). 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	0.091
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.83
DEOGEN2	Benign	0.26	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.028	N
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.069	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.0	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.057
Sift	Benign	0.53	T;T
Sift4G	Benign	0.77	T;T
Polyphen		0.0	B;B
Vest4		0.21
MutPred		0.62		Loss of stability (P = 0.0024);Loss of stability (P = 0.0024);
MVP		0.18
MPC		0.59
ClinPred		0.060	T
GERP RS		0.23
Varity_R		0.15
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-38158589;