chr13-99982139-CGCG-C

Variant names:

• chr13-99982139-CGCG-C
• rs748109787
• NM_007129.5:c.90_92delGGC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP3 BP6 BS2

The NM_007129.5(ZIC2):​c.90_92delGGC​(p.Ala31del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000616 in 1,175,406 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00062 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZIC2 NM_007129.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61

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 Likely_benign. Variant got -6 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_007129.5
• BP6: Variant 13-99982139-CGCG-C is Benign according to our data. Variant chr13-99982139-CGCG-C is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAdExome4 at 724 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZIC2	NM_007129.5	c.90_92delGGC	p.Ala31del	disruptive_inframe_deletion	Exon 1 of 3	ENST00000376335.8	NP_009060.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZIC2	ENST00000376335.8	c.90_92delGGC	p.Ala31del	disruptive_inframe_deletion	Exon 1 of 3	1	NM_007129.5	ENSP00000365514.3

Frequencies

GnomAD3 genomes AF: 0.00000663 AC: 1 AN: 150788 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000243

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

GnomAD3 exomes AF: 0.00357 AC: 93 AN: 26028 Hom.: 0 AF XY: 0.00331 AC XY: 53 AN XY: 15988

Gnomad AFR exome AF: 0.000956

Gnomad AMR exome AF: 0.00628

Gnomad ASJ exome AF: 0.00266

Gnomad EAS exome AF: 0.00149

Gnomad SAS exome AF: 0.00488

Gnomad FIN exome AF: 0.00423

Gnomad NFE exome AF: 0.00302

Gnomad OTH exome AF: 0.00772

GnomAD4 exome AF: 0.000616 AC: 724 AN: 1175406 Hom.: 0 AF XY: 0.000798 AC XY: 453 AN XY: 567682

Gnomad4 AFR exome AF: 0.000253

Gnomad4 AMR exome AF: 0.00158

Gnomad4 ASJ exome AF: 0.000542

Gnomad4 EAS exome AF: 0.000183

Gnomad4 SAS exome AF: 0.00462

Gnomad4 FIN exome AF: 0.00140

Gnomad4 NFE exome AF: 0.000413

Gnomad4 OTH exome AF: 0.000945

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000663 AC: 1 AN: 150788 Hom.: 0 Cov.: 31 AF XY: 0.0000136 AC XY: 1 AN XY: 73622

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Asia WGS AF: 0.00177 AC: 6 AN: 3414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs748109787; hg19: chr13-100634393;