2-206297282-C-G

Variant names:

• chr2-206297282-C-G
• rs1190672560
• NM_020923.3:c.97C>G

Variant summary

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

The NM_020923.3(ZDBF2):​c.97C>G​(p.Gln33Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000711 in 1,406,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: ZDBF2 NM_020923.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22

Genes affected

ZDBF2 (HGNC:29313): (zinc finger DBF-type containing 2) This gene encodes a protein containing DBF4-type zinc finger domains. This gene is imprinted and paternally expressed in lymphocytes but is more stochastically expressed in the placenta. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

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=0.11838892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDBF2	NM_020923.3	c.97C>G	p.Gln33Glu	missense_variant	Exon 4 of 5	ENST00000374423.9	NP_065974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDBF2	ENST00000374423.9	c.97C>G	p.Gln33Glu	missense_variant	Exon 4 of 5	1	NM_020923.3	ENSP00000363545.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248904 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 135020

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000711 AC: 10 AN: 1406502 Hom.: 0 Cov.: 24 AF XY: 0.00000853 AC XY: 6 AN XY: 703210

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000848

Gnomad4 OTH exome AF: 0.0000171

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000935 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 02, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.97C>G (p.Q33E) alteration is located in exon 4 (coding exon 2) of the ZDBF2 gene. This alteration results from a C to G substitution at nucleotide position 97, causing the glutamine (Q) at amino acid position 33 to be replaced by a glutamic acid (E). 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	0.10
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.0068	T;T;.;.;.;.;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.26	N
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.12	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;.;.;.;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.5	N;.;.;.;.;.;.
REVEL	Benign	0.027
Sift	Benign	0.11	T;.;.;.;.;.;.
Sift4G	Uncertain	0.020	D;.;.;.;.;.;D
Polyphen		0.12	B;B;.;.;.;.;.
Vest4		0.35
MutPred		0.58		Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);.;
MVP		0.15
MPC		0.088
ClinPred		0.042	T
GERP RS		2.5
Varity_R		0.088
gMVP		0.033

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: rs1190672560; hg19: chr2-207162006;