chr7-39252512-G-T

Variant names:

• chr7-39252512-G-T
• rs9655034
• NM_001370959.1:c.598+44892G>T

Variant summary

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

The NM_001370959.1(POU6F2):​c.598+44892G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 151,668 control chromosomes in the GnomAD database, including 12,623 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 0.39 (12623 hom., cov: 30)
• Consequence: POU6F2 NM_001370959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280
• Publications: 4 publications found

Genes affected

POU6F2 (HGNC:21694): (POU class 6 homeobox 2) This gene encodes a member of the POU protein family characterized by the presence of a bipartite DNA binding domain, consisting of a POU-specific domain and a homeodomain, separated by a variable polylinker. The DNA binding domain may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner. The POU family members are transcriptional regulators, many of which are known to control cell type-specific differentiation pathways. This gene is a tumor suppressor involved in Wilms tumor (WT) predisposition. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

POU6F2 Gene-Disease associations (from GenCC):

• Wilms tumor 5

  Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370959.1. 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
	POU6F2	NM_001370959.1	MANE Select	c.598+44892G>T		intron	N/A	NP_001357888.1
	POU6F2	NM_007252.4		c.511+44892G>T		intron	N/A	NP_009183.3
	POU6F2	NM_001166018.2		c.511+44892G>T		intron	N/A	NP_001159490.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU6F2	ENST00000518318.7	TSL:1 MANE Select	c.598+44892G>T		intron	N/A	ENSP00000430514.3
	POU6F2	ENST00000403058.6	TSL:5	c.511+44892G>T		intron	N/A	ENSP00000384004.1
	POU6F2	ENST00000517348.1	TSL:2	n.972+44892G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59289 AN: 151546 Hom.: 12624 Cov.: 30

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.340

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.379

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

GnomAD4 genome AF: 0.391 AC: 59295 AN: 151668 Hom.: 12623 Cov.: 30 AF XY: 0.394 AC XY: 29161 AN XY: 74102

African (AFR) AF: 0.217 AC: 8966 AN: 41316

American (AMR) AF: 0.388 AC: 5914 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1570 AN: 3470

East Asian (EAS) AF: 0.685 AC: 3518 AN: 5138

South Asian (SAS) AF: 0.370 AC: 1774 AN: 4800

European-Finnish (FIN) AF: 0.475 AC: 5006 AN: 10544

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.460 AC: 31243 AN: 67862

Other (OTH) AF: 0.376 AC: 790 AN: 2102

Alfa AF: 0.431 Hom.: 45861

Bravo AF: 0.382

Asia WGS AF: 0.490 AC: 1701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.4
DANN	Benign	0.81
PhyloP100		0.028
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: rs9655034; hg19: chr7-39292111;