2-206304875-A-G

Variant names:

• chr2-206304875-A-G
• rs754236342
• NM_020923.3:c.347A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020923.3(ZDBF2):​c.347A>G​(p.Glu116Gly) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E116V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZDBF2 NM_020923.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58
• Publications: 1 publications found

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]

ZDBF2 Gene-Disease associations (from GenCC):

• nasopalpebral lipoma-coloboma syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08746365).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020923.3. 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
	ZDBF2	NM_020923.3	MANE Select	c.347A>G	p.Glu116Gly	missense	Exon 5 of 5	NP_065974.1	Q9HCK1
	ZDBF2	NM_001369654.1		c.347A>G	p.Glu116Gly	missense	Exon 6 of 6	NP_001356583.1	N0DVB2
	ZDBF2	NM_001285549.2		c.341A>G	p.Glu114Gly	missense	Exon 7 of 7	NP_001272478.1	N0DVX5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDBF2	ENST00000374423.9	TSL:1 MANE Select	c.347A>G	p.Glu116Gly	missense	Exon 5 of 5	ENSP00000363545.3	Q9HCK1
	ZDBF2	ENST00000649650.1		c.347A>G	p.Glu116Gly	missense	Exon 6 of 6	ENSP00000497308.1	Q9HCK1
	ZDBF2	ENST00000920103.1		c.347A>G	p.Glu116Gly	missense	Exon 6 of 6	ENSP00000590162.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.29	N
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.6
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.063
Sift	Uncertain	0.011	D
Sift4G	Benign	0.091	T
Polyphen		0.015	B
Vest4		0.12
MutPred		0.15		Loss of stability (P = 0.0652)
MVP		0.22
MPC		0.16
ClinPred		0.42	T
GERP RS		2.6
Varity_R		0.064
gMVP		0.089
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs754236342; hg19: chr2-207169599;