rs2108720

Positions:

• chr7-39441302-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370959.1(POU6F2):​c.1320+8019G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,332 control chromosomes in the GnomAD database, including 9,590 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 0.34 (9590 hom., cov: 30)
• Consequence: POU6F2 NM_001370959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133

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]

LOC105375238 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU6F2	NM_001370959.1	c.1320+8019G>A		intron_variant		ENST00000518318.7
LOC105375238	XR_927186.2	n.172-24938C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU6F2	ENST00000518318.7	c.1320+8019G>A		intron_variant		1	NM_001370959.1	P2

Frequencies

GnomAD3 genomes AF: 0.337 AC: 50899 AN: 151214 Hom.: 9559 Cov.: 30

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.276

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.337 AC: 50986 AN: 151332 Hom.: 9590 Cov.: 30 AF XY: 0.339 AC XY: 25036 AN XY: 73832

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.337

Alfa AF: 0.275 Hom.: 2885

Bravo AF: 0.348

Asia WGS AF: 0.452 AC: 1568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs2108720; hg19: chr7-39480901;