8-105064469-C-T

Variant names:

• chr8-105064469-C-T
• rs285790
• ENST00000518180.1:n.242+72800C>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+72800C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.923 in 152,268 control chromosomes in the GnomAD database, including 65,096 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 0.92 (65096 hom., cov: 32)
• Consequence: ZFPM2 ENST00000518180.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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+72800C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.923 AC: 140478 AN: 152150 Hom.: 65035 Cov.: 32

Gnomad AFR AF: 0.974

Gnomad AMI AF: 0.950

Gnomad AMR AF: 0.916

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.959

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.915

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

GnomAD4 genome AF: 0.923 AC: 140598 AN: 152268 Hom.: 65096 Cov.: 32 AF XY: 0.927 AC XY: 69033 AN XY: 74442

African (AFR) AF: 0.974 AC: 40475 AN: 41558

American (AMR) AF: 0.916 AC: 14003 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3157 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5178 AN: 5186

South Asian (SAS) AF: 0.932 AC: 4492 AN: 4822

European-Finnish (FIN) AF: 0.959 AC: 10167 AN: 10606

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.883 AC: 60048 AN: 68018

Other (OTH) AF: 0.915 AC: 1937 AN: 2116

Alfa AF: 0.898 Hom.: 30970

Bravo AF: 0.924

Asia WGS AF: 0.962 AC: 3345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.089
DANN	Benign	0.19
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs285790; hg19: chr8-106076697;