chr8-105318866-G-GGCGGCGGGA

Variant names:

• chr8-105318866-G-GGCGGCGGGA
• rs71305140
• NM_012082.4:c.-73_-65dupGGCGGGAGC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_012082.4(ZFPM2):​c.-73_-65dupGGCGGGAGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.84 (51088 hom., cov: 0)
  • Exomes 𝑓: 0.76 (187936 hom.)
• Consequence: ZFPM2 NM_012082.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.37
• 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 -10 ACMG points.

• BP6: Variant 8-105318866-G-GGCGGCGGGA is Benign according to our data. Variant chr8-105318866-G-GGCGGCGGGA is described in ClinVar as [Benign]. Clinvar id is 1233669.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFPM2	NM_012082.4	c.-73_-65dupGGCGGGAGC		5_prime_UTR_variant	Exon 1 of 8	ENST00000407775.7	NP_036214.2
ZFPM2	NM_001362836.2	c.-73_-65dupGGCGGGAGC		5_prime_UTR_variant	Exon 1 of 7		NP_001349765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFPM2	ENST00000407775.7	c.-73_-65dupGGCGGGAGC		5_prime_UTR_variant	Exon 1 of 8	1	NM_012082.4	ENSP00000384179.2
ZFPM2	ENST00000518180.1	n.479+72340_479+72348dupGGCGGGAGC		intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes AF: 0.836 AC: 121884 AN: 145846 Hom.: 51051 Cov.: 0

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.876

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.849

GnomAD4 exome AF: 0.755 AC: 506434 AN: 670558 Hom.: 187936 Cov.: 13 AF XY: 0.754 AC XY: 237842 AN XY: 315646

African (AFR) AF: 0.787 AC: 8811 AN: 11192

American (AMR) AF: 0.784 AC: 806 AN: 1028

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 3327 AN: 4246

East Asian (EAS) AF: 0.869 AC: 3109 AN: 3578

South Asian (SAS) AF: 0.798 AC: 10993 AN: 13784

European-Finnish (FIN) AF: 0.824 AC: 5929 AN: 7194

Middle Eastern (MID) AF: 0.825 AC: 1086 AN: 1316

European-Non Finnish (NFE) AF: 0.751 AC: 455588 AN: 606480

Other (OTH) AF: 0.772 AC: 16785 AN: 21740

GnomAD4 genome AF: 0.836 AC: 121967 AN: 145942 Hom.: 51088 Cov.: 0 AF XY: 0.841 AC XY: 59679 AN XY: 70954

African (AFR) AF: 0.824 AC: 33578 AN: 40766

American (AMR) AF: 0.873 AC: 12868 AN: 14740

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2855 AN: 3382

East Asian (EAS) AF: 0.946 AC: 4554 AN: 4812

South Asian (SAS) AF: 0.881 AC: 4215 AN: 4786

European-Finnish (FIN) AF: 0.888 AC: 7599 AN: 8558

Middle Eastern (MID) AF: 0.870 AC: 247 AN: 284

European-Non Finnish (NFE) AF: 0.815 AC: 53532 AN: 65674

Other (OTH) AF: 0.848 AC: 1726 AN: 2036

Alfa AF: 0.703 Hom.: 1334

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4
Mutation Taster		=299/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs71305140; hg19: chr8-106331094;