rs285778

Variant names:

• chr8-105099728-C-T
• rs285778
• ENST00000518180.1:n.242+108059C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000518180.1(ZFPM2):​n.242+108059C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 152,172 control chromosomes in the GnomAD database, including 54,347 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 0.84 (54347 hom., cov: 32)
• Consequence: ZFPM2 ENST00000518180.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325
• Publications: 1 publications found

Genes affected

ZFPM2 (HGNC:16700): (zinc finger protein, FOG family member 2) The zinc finger protein encoded by this gene is a widely expressed member of the FOG family of transcription factors. The family members modulate the activity of GATA family proteins, which are important regulators of hematopoiesis and cardiogenesis in mammals. It has been demonstrated that the protein can both activate and down-regulate expression of GATA-target genes, suggesting different modulation in different promoter contexts. A related mRNA suggests an alternatively spliced product but this information is not yet fully supported by the sequence. [provided by RefSeq, Jul 2008]

ZFPM2 Gene-Disease associations (from GenCC):

• 46,XY sex reversal 9

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• diaphragmatic hernia 3

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• tetralogy of fallot

  Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 46,XY partial gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000518180.1	n.242+108059C>T		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.842 AC: 128000 AN: 152054 Hom.: 54317 Cov.: 32

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.977

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.938

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.860

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.842 AC: 128084 AN: 152172 Hom.: 54347 Cov.: 32 AF XY: 0.847 AC XY: 62976 AN XY: 74388

African (AFR) AF: 0.742 AC: 30789 AN: 41486

American (AMR) AF: 0.885 AC: 13524 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3043 AN: 3468

East Asian (EAS) AF: 0.998 AC: 5169 AN: 5178

South Asian (SAS) AF: 0.938 AC: 4525 AN: 4826

European-Finnish (FIN) AF: 0.909 AC: 9640 AN: 10608

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.859 AC: 58414 AN: 68014

Other (OTH) AF: 0.861 AC: 1817 AN: 2110

Alfa AF: 0.843 Hom.: 11700

Bravo AF: 0.837

Asia WGS AF: 0.950 AC: 3305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.82
DANN	Benign	0.50
PhyloP100		-0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs285778; hg19: chr8-106111956;