rs285866

Variant names:

• chr8-105051229-A-G
• rs285866
• ENST00000518180.1:n.242+59560A>G

Variant summary

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

The ENST00000518180.1(ZFPM2):​n.242+59560A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,094 control chromosomes in the GnomAD database, including 9,979 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 0.33 (9979 hom., cov: 33)
• Consequence: ZFPM2 ENST00000518180.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.887
• 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: 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.427 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+59560A>G		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50118 AN: 151976 Hom.: 9984 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.330 AC: 50115 AN: 152094 Hom.: 9979 Cov.: 33 AF XY: 0.331 AC XY: 24607 AN XY: 74322

African (AFR) AF: 0.108 AC: 4474 AN: 41546

American (AMR) AF: 0.431 AC: 6581 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1530 AN: 3470

East Asian (EAS) AF: 0.212 AC: 1096 AN: 5182

South Asian (SAS) AF: 0.442 AC: 2132 AN: 4826

European-Finnish (FIN) AF: 0.359 AC: 3792 AN: 10564

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.431 AC: 29257 AN: 67926

Other (OTH) AF: 0.353 AC: 745 AN: 2112

Alfa AF: 0.371 Hom.: 2042

Bravo AF: 0.325

Asia WGS AF: 0.283 AC: 979 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.63
DANN	Benign	0.53
PhyloP100		-0.89

Splicing

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

Other links and lift over

dbSNP: rs285866; hg19: chr8-106063457;