chr2-173354978-C-T

Variant names:

• chr2-173354978-C-T
• NM_031942.5:c.15C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_031942.5(CDCA7):​c.15C>T​(p.Arg5Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000775 in 1,290,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: CDCA7 NM_031942.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.496
• Publications: 0 publications found

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]

CDCA7 Gene-Disease associations (from GenCC):

• immunodeficiency-centromeric instability-facial anomalies syndrome 3

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• immunodeficiency-centromeric instability-facial anomalies syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000293276 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 2-173354978-C-T is Benign according to our data. Variant chr2-173354978-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2789150.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.496 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031942.5. 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
	CDCA7	NM_031942.5	MANE Select	c.15C>T	p.Arg5Arg	synonymous	Exon 1 of 10	NP_114148.3
	CDCA7	NM_145810.3		c.15C>T	p.Arg5Arg	synonymous	Exon 1 of 9	NP_665809.1	Q9BWT1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDCA7	ENST00000306721.8	TSL:2 MANE Select	c.15C>T	p.Arg5Arg	synonymous	Exon 1 of 10	ENSP00000306968.3	Q9BWT1-2
	CDCA7	ENST00000347703.7	TSL:1	c.15C>T	p.Arg5Arg	synonymous	Exon 1 of 9	ENSP00000272789.4	Q9BWT1-1
	CDCA7	ENST00000467411.5	TSL:1	n.86C>T		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.75e-7 AC: 1 AN: 1290612 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 635018

African (AFR) AF: 0.00 AC: 0 AN: 25920

American (AMR) AF: 0.00 AC: 0 AN: 21168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21478

East Asian (EAS) AF: 0.0000357 AC: 1 AN: 27982

South Asian (SAS) AF: 0.00 AC: 0 AN: 66118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3824

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1038096

Other (OTH) AF: 0.00 AC: 0 AN: 53406

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	15
DANN	Uncertain	0.98
PhyloP100		0.50
PromoterAI		0.037	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	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: chr2-174219706;