chr13-99986138-G-A

Position:

• chr13-99986138-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007129.5(ZIC2):​c.*456G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 441,306 control chromosomes in the GnomAD database, including 16,691 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (7662 hom., cov: 32)
  • Exomes 𝑓: 0.24 (9029 hom.)
• Consequence: ZIC2 NM_007129.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

Genes affected

ZIC2 (HGNC:12873): (Zic family member 2) This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. This protein functions as a transcriptional repressor and may regulate tissue specific expression of dopamine receptor D1. Expansion of an alanine repeat in the C-terminus of the encoded protein and other mutations in this gene cause holoprosencephaly type 5. Holoprosencephaly is the most common structural anomaly of the human brain. A polyhistidine tract polymorphism in this gene may be associated with increased risk of neural tube defects. This gene is closely linked to a gene encoding zinc finger protein of the cerebellum 5, a related family member on chromosome 13. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZIC2	NM_007129.5	c.*456G>A		3_prime_UTR_variant	3/3	ENST00000376335.8	NP_009060.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZIC2	ENST00000376335.8	c.*456G>A		3_prime_UTR_variant	3/3	1	NM_007129.5	ENSP00000365514	P1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45560 AN: 151894 Hom.: 7650 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.321

GnomAD4 exome AF: 0.242 AC: 70089 AN: 289294 Hom.: 9029 Cov.: 0 AF XY: 0.239 AC XY: 39506 AN XY: 165210

Gnomad4 AFR exome AF: 0.470

Gnomad4 AMR exome AF: 0.263

Gnomad4 ASJ exome AF: 0.311

Gnomad4 EAS exome AF: 0.282

Gnomad4 SAS exome AF: 0.222

Gnomad4 FIN exome AF: 0.181

Gnomad4 NFE exome AF: 0.230

Gnomad4 OTH exome AF: 0.261

GnomAD4 genome AF: 0.300 AC: 45601 AN: 152012 Hom.: 7662 Cov.: 32 AF XY: 0.297 AC XY: 22066 AN XY: 74308

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.323

Alfa AF: 0.248 Hom.: 7840

Bravo AF: 0.314

Asia WGS AF: 0.296 AC: 1028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.78
DANN	Benign	0.72

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: rs13542; hg19: chr13-100638392;