rs876657409

Positions:

• chr2-173366363-AG-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_031942.5(CDCA7):​c.1118del​(p.Gly373AlafsTer54) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDCA7 NM_031942.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 10.0

Genes affected

CDCA7 (HGNC:14628): (cell division cycle associated 7) This gene was identified as a c-Myc responsive gene, and behaves as a direct c-Myc target gene. Overexpression of this gene is found to enhance the transformation of lymphoblastoid cells, and it complements a transformation-defective Myc Box II mutant, suggesting its involvement in c-Myc-mediated cell transformation. Two alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-173366363-AG-A is Pathogenic according to our data. Variant chr2-173366363-AG-A is described in ClinVar as [Pathogenic]. Clinvar id is 225530.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDCA7	NM_031942.5	c.1118del	p.Gly373AlafsTer54	frameshift_variant	8/10	ENST00000306721.8	NP_114148.3
CDCA7	NM_145810.3	c.881del	p.Gly294AlafsTer54	frameshift_variant	7/9		NP_665809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDCA7	ENST00000306721.8	c.1118del	p.Gly373AlafsTer54	frameshift_variant	8/10	2	NM_031942.5	ENSP00000306968	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Immunodeficiency-centromeric instability-facial anomalies syndrome 3 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs876657409; hg19: chr2-174231091;