chr7-39433109-A-G

Variant names:

• chr7-39433109-A-G
• rs2302123
• NM_001370959.1:c.1146A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001370959.1(POU6F2):​c.1146A>G​(p.Pro382Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,613,304 control chromosomes in the GnomAD database, including 69,266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.35 (10438 hom., cov: 31)
  • Exomes 𝑓: 0.28 (58828 hom.)
• Consequence: POU6F2 NM_001370959.1 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0360
• Publications: 16 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-39433109-A-G is Benign according to our data. Variant chr7-39433109-A-G is described in ClinVar as Benign. ClinVar VariationId is 3060957.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.036 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU6F2	NM_001370959.1	MANE Select	c.1146A>G	p.Pro382Pro	synonymous	Exon 7 of 10	NP_001357888.1	A0A6E1XZL4
	POU6F2	NM_007252.4		c.1059A>G	p.Pro353Pro	synonymous	Exon 8 of 11	NP_009183.3	P78424-1
	POU6F2	NM_001166018.2		c.1059A>G	p.Pro353Pro	synonymous	Exon 8 of 11	NP_001159490.1	P78424-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU6F2	ENST00000518318.7	TSL:1 MANE Select	c.1146A>G	p.Pro382Pro	synonymous	Exon 7 of 10	ENSP00000430514.3	A0A6E1XZL4
	POU6F2	ENST00000403058.6	TSL:5	c.1059A>G	p.Pro353Pro	synonymous	Exon 8 of 11	ENSP00000384004.1	P78424-1
	POU6F2	ENST00000416452.1	TSL:5	n.156A>G		non_coding_transcript_exon	Exon 2 of 4	ENSP00000404868.1	H7C2B2

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52551 AN: 151570 Hom.: 10399 Cov.: 31

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.337

GnomAD2 exomes AF: 0.312 AC: 78073 AN: 250452 AF XY: 0.302

Gnomad AFR exome AF: 0.521

Gnomad AMR exome AF: 0.322

Gnomad ASJ exome AF: 0.293

Gnomad EAS exome AF: 0.583

Gnomad FIN exome AF: 0.273

Gnomad NFE exome AF: 0.256

Gnomad OTH exome AF: 0.294

GnomAD4 exome AF: 0.275 AC: 402239 AN: 1461618 Hom.: 58828 Cov.: 37 AF XY: 0.273 AC XY: 198759 AN XY: 727098

African (AFR) AF: 0.524 AC: 17559 AN: 33480

American (AMR) AF: 0.323 AC: 14456 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 7671 AN: 26136

East Asian (EAS) AF: 0.572 AC: 22724 AN: 39700

South Asian (SAS) AF: 0.272 AC: 23447 AN: 86256

European-Finnish (FIN) AF: 0.276 AC: 14706 AN: 53378

Middle Eastern (MID) AF: 0.217 AC: 1251 AN: 5768

European-Non Finnish (NFE) AF: 0.254 AC: 282411 AN: 1111806

Other (OTH) AF: 0.298 AC: 18014 AN: 60372

GnomAD4 genome AF: 0.347 AC: 52647 AN: 151686 Hom.: 10438 Cov.: 31 AF XY: 0.349 AC XY: 25842 AN XY: 74088

African (AFR) AF: 0.525 AC: 21671 AN: 41280

American (AMR) AF: 0.308 AC: 4708 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 998 AN: 3468

East Asian (EAS) AF: 0.583 AC: 2958 AN: 5074

South Asian (SAS) AF: 0.286 AC: 1370 AN: 4790

European-Finnish (FIN) AF: 0.273 AC: 2878 AN: 10542

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17168 AN: 67956

Other (OTH) AF: 0.343 AC: 723 AN: 2108

Alfa AF: 0.287 Hom.: 28504

Bravo AF: 0.361

Asia WGS AF: 0.472 AC: 1637 AN: 3478

EpiCase AF: 0.251

EpiControl AF: 0.248

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	POU6F2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.38
DANN	Benign	0.42
PhyloP100		-0.036
Mutation Taster		=99/1	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: rs2302123; hg19: chr7-39472708; COSMIC: COSV68873863;