chr2-206304914-A-T

Variant names:

• chr2-206304914-A-T
• rs113954798
• NM_020923.3:c.386A>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_020923.3(ZDBF2):​c.386A>T​(p.Gln129Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,613,716 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 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. Q129R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000059 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (4 hom.)
• Consequence: ZDBF2 NM_020923.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 2 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08138198).
• BS2: High AC in GnomAd4 at 9 Unknown,AD gene.

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.386A>T	p.Gln129Leu	missense	Exon 5 of 5	NP_065974.1	Q9HCK1
	ZDBF2	NM_001369654.1		c.386A>T	p.Gln129Leu	missense	Exon 6 of 6	NP_001356583.1	N0DVB2
	ZDBF2	NM_001285549.2		c.380A>T	p.Gln127Leu	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.386A>T	p.Gln129Leu	missense	Exon 5 of 5	ENSP00000363545.3	Q9HCK1
	ZDBF2	ENST00000649650.1		c.386A>T	p.Gln129Leu	missense	Exon 6 of 6	ENSP00000497308.1	Q9HCK1
	ZDBF2	ENST00000920103.1		c.386A>T	p.Gln129Leu	missense	Exon 6 of 6	ENSP00000590162.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152156 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000804 AC: 2 AN: 248664 AF XY: 0.00000741

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000397 AC: 58 AN: 1461442 Hom.: 4 Cov.: 30 AF XY: 0.0000454 AC XY: 33 AN XY: 727004

African (AFR) AF: 0.000747 AC: 25 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111752

Other (OTH) AF: 0.000547 AC: 33 AN: 60364

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152274 Hom.: 1 Cov.: 32 AF XY: 0.0000940 AC XY: 7 AN XY: 74466

African (AFR) AF: 0.000216 AC: 9 AN: 41586

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 6

Bravo AF: 0.0000302

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.6
DANN	Benign	0.95
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.11	N
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.4
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.027
Sift	Benign	0.045	D
Sift4G	Benign	0.17	T
Polyphen		0.020	B
Vest4		0.16
MutPred		0.23		Gain of sheet (P = 0.0125)
MVP		0.24
MPC		0.057
ClinPred		0.039	T
GERP RS		1.0
Varity_R		0.064
gMVP		0.083
Mutation Taster		=100/0	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

dbSNP: rs113954798; hg19: chr2-207169638;