2-206304824-A-T

Variant names:

• chr2-206304824-A-T
• rs149317779
• NM_020923.3:c.296A>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_020923.3(ZDBF2):​c.296A>T​(p.Asp99Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,613,726 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (10 hom.)
• Consequence: ZDBF2 NM_020923.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.250
• Publications: 6 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005754411).
• BP6: Variant 2-206304824-A-T is Benign according to our data. Variant chr2-206304824-A-T is described in ClinVar as Benign. ClinVar VariationId is 2823821.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 161 AD,Unknown 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.296A>T	p.Asp99Val	missense	Exon 5 of 5	NP_065974.1	Q9HCK1
	ZDBF2	NM_001369654.1		c.296A>T	p.Asp99Val	missense	Exon 6 of 6	NP_001356583.1	N0DVB2
	ZDBF2	NM_001285549.2		c.290A>T	p.Asp97Val	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.296A>T	p.Asp99Val	missense	Exon 5 of 5	ENSP00000363545.3	Q9HCK1
	ZDBF2	ENST00000649650.1		c.296A>T	p.Asp99Val	missense	Exon 6 of 6	ENSP00000497308.1	Q9HCK1
	ZDBF2	ENST00000920103.1		c.296A>T	p.Asp99Val	missense	Exon 6 of 6	ENSP00000590162.1

Frequencies

GnomAD3 genomes AF: 0.00106 AC: 161 AN: 152074 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00519

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00175 AC: 435 AN: 249022 AF XY: 0.00208

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00156

Gnomad OTH exome AF: 0.00182

GnomAD4 exome AF: 0.00132 AC: 1932 AN: 1461534 Hom.: 10 Cov.: 30 AF XY: 0.00152 AC XY: 1106 AN XY: 727036

African (AFR) AF: 0.0000896 AC: 3 AN: 33470

American (AMR) AF: 0.00110 AC: 49 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.00748 AC: 645 AN: 86250

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53398

Middle Eastern (MID) AF: 0.0106 AC: 61 AN: 5762

European-Non Finnish (NFE) AF: 0.000971 AC: 1080 AN: 1111772

Other (OTH) AF: 0.00149 AC: 90 AN: 60372

GnomAD4 genome AF: 0.00106 AC: 161 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.00102 AC XY: 76 AN XY: 74408

African (AFR) AF: 0.000289 AC: 12 AN: 41534

American (AMR) AF: 0.00118 AC: 18 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00519 AC: 25 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00125 AC: 85 AN: 68004

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00157 Hom.: 2

Bravo AF: 0.00106

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00132 AC: 11

ExAC AF: 0.00182 AC: 220

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00289

EpiControl AF: 0.00243

ClinVar

ClinVar submissions

Significance: 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
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.1
DANN	Benign	0.76
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.37	N
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.25
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.059
Sift	Benign	0.085	T
Sift4G	Uncertain	0.033	D
Polyphen		0.65	P
Vest4		0.21
MVP		0.21
MPC		0.34
ClinPred		0.035	T
GERP RS		1.5
Varity_R		0.11
gMVP		0.040
Mutation Taster		=99/1	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: rs149317779; hg19: chr2-207169548;