8-105497747-G-A

Variant names:

• chr8-105497747-G-A
• rs2622633
• NM_012082.4:c.301+53366G>A

Variant summary

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

The NM_012082.4(ZFPM2):​c.301+53366G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 151,992 control chromosomes in the GnomAD database, including 4,569 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 0.24 (4569 hom., cov: 31)
• Consequence: ZFPM2 NM_012082.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.949
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012082.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM2	NM_012082.4	MANE Select	c.301+53366G>A		intron	N/A	NP_036214.2
	ZFPM2	NM_001362836.2		c.142+53366G>A		intron	N/A	NP_001349765.1
	ZFPM2	NM_001362837.2		c.-96+53366G>A		intron	N/A	NP_001349766.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFPM2	ENST00000407775.7	TSL:1 MANE Select	c.301+53366G>A		intron	N/A	ENSP00000384179.2
	ZFPM2	ENST00000511341.6	TSL:1	n.1041+53366G>A		intron	N/A
	ZFPM2	ENST00000520492.5	TSL:2	c.-96+53366G>A		intron	N/A	ENSP00000430757.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36712 AN: 151874 Hom.: 4558 Cov.: 31

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.0914

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.242 AC: 36752 AN: 151992 Hom.: 4569 Cov.: 31 AF XY: 0.242 AC XY: 17946 AN XY: 74282

African (AFR) AF: 0.202 AC: 8356 AN: 41442

American (AMR) AF: 0.263 AC: 4014 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 917 AN: 3468

East Asian (EAS) AF: 0.0926 AC: 478 AN: 5162

South Asian (SAS) AF: 0.301 AC: 1448 AN: 4810

European-Finnish (FIN) AF: 0.259 AC: 2731 AN: 10558

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 18028 AN: 67984

Other (OTH) AF: 0.237 AC: 502 AN: 2114

Alfa AF: 0.258 Hom.: 6663

Bravo AF: 0.238

Asia WGS AF: 0.190 AC: 664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.67
DANN	Benign	0.74
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2622633; hg19: chr8-106509975;