rs285814

Variant names:

• chr8-105096256-T-C
• rs285814
• ENST00000518180.1:n.242+104587T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000518180.1(ZFPM2):​n.242+104587T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,008 control chromosomes in the GnomAD database, including 9,898 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 0.34 (9898 hom., cov: 32)
• Consequence: ZFPM2 ENST00000518180.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.20
• 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: G2P, Labcorp Genetics (formerly Invitae)
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000518180.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM2	ENST00000518180.1	TSL:4	n.242+104587T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51121 AN: 151888 Hom.: 9903 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.336 AC: 51124 AN: 152008 Hom.: 9898 Cov.: 32 AF XY: 0.335 AC XY: 24916 AN XY: 74294

African (AFR) AF: 0.152 AC: 6328 AN: 41504

American (AMR) AF: 0.430 AC: 6556 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1439 AN: 3468

East Asian (EAS) AF: 0.200 AC: 1034 AN: 5164

South Asian (SAS) AF: 0.392 AC: 1892 AN: 4822

European-Finnish (FIN) AF: 0.343 AC: 3629 AN: 10572

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29089 AN: 67924

Other (OTH) AF: 0.350 AC: 739 AN: 2110

Alfa AF: 0.366 Hom.: 1450

Bravo AF: 0.335

Asia WGS AF: 0.269 AC: 937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Benign	0.79
PhyloP100		3.2

Splicing

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

Other links and lift over

dbSNP: rs285814; hg19: chr8-106108484;