rs2108720

Variant names:

• chr7-39441302-G-A
• rs2108720
• NM_001370959.1:c.1320+8019G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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]

YAE1-DT (HGNC:55820): (YAE1 divergent transcript)

LOC105375238 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
POU6F2	NM_001370959.1	c.1320+8019G>A		intron_variant	Intron 7 of 9	ENST00000518318.7	NP_001357888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU6F2	ENST00000518318.7	c.1320+8019G>A		intron_variant	Intron 7 of 9	1	NM_001370959.1	ENSP00000430514.3

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

African (AFR) AF: 0.479 AC: 19720 AN: 41130

American (AMR) AF: 0.307 AC: 4678 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 998 AN: 3466

East Asian (EAS) AF: 0.583 AC: 2998 AN: 5142

South Asian (SAS) AF: 0.271 AC: 1296 AN: 4788

European-Finnish (FIN) AF: 0.285 AC: 2968 AN: 10402

Middle Eastern (MID) AF: 0.283 AC: 82 AN: 290

European-Non Finnish (NFE) AF: 0.257 AC: 17450 AN: 67886

Other (OTH) AF: 0.337 AC: 705 AN: 2092

Alfa AF: 0.277 Hom.: 3274

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
PhyloP100		0.13
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: rs2108720; hg19: chr7-39480901;