Variant 7-39339688-CCAG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP3BP6BS1BS2

The NM_001370959.1(POU6F2):c.674_676del(p.Gln225del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00547 in 1,416,950 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 0 hom. )

Consequence

POU6F2
NM_001370959.1 inframe_deletion

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.10

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001370959.1

BP6

Variant 7-39339688-CCAG-C is Benign according to our data. Variant chr7-39339688-CCAG-C is described in ClinVar as [Benign]. Clinvar id is 3060981.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00609 (7702/1265678) while in subpopulation AMR AF= 0.0208 (748/36048). AF 95% confidence interval is 0.0195. There are 0 homozygotes in gnomad4_exome. There are 4369 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

BS2

High AC in GnomAd4 at 50 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU6F2	NM_001370959.1 linkuse as main transcript	c.674_676del	p.Gln225del	inframe_deletion	5/10	ENST00000518318.7	NP_001357888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU6F2	ENST00000518318.7 linkuse as main transcript	c.674_676del	p.Gln225del	inframe_deletion	5/10	1	NM_001370959.1	ENSP00000430514	P2

Frequencies

GnomAD3 genomes

AF:

0.000331

AC:

AN:

151164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000970

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000724

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000418

Gnomad FIN

AF:

0.000291

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000428

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0295

AC:

4811

AN:

163196

Hom.:

AF XY:

0.0307

AC XY:

2725

AN XY:

88804

show subpopulations

Gnomad AFR exome

AF:

0.0215

Gnomad AMR exome

AF:

0.0316

Gnomad ASJ exome

AF:

0.0351

Gnomad EAS exome

AF:

0.0219

Gnomad SAS exome

AF:

0.0355

Gnomad FIN exome

AF:

0.0290

Gnomad NFE exome

AF:

0.0294

Gnomad OTH exome

AF:

0.0279

GnomAD4 exome

AF:

0.00609

AC:

7702

AN:

1265678

Hom.:

AF XY:

0.00699

AC XY:

4369

AN XY:

625128

show subpopulations

Gnomad4 AFR exome

AF:

0.00707

Gnomad4 AMR exome

AF:

0.0208

Gnomad4 ASJ exome

AF:

0.0130

Gnomad4 EAS exome

AF:

0.00597

Gnomad4 SAS exome

AF:

0.0169

Gnomad4 FIN exome

AF:

0.0132

Gnomad4 NFE exome

AF:

0.00437

Gnomad4 OTH exome

AF:

0.00604

GnomAD4 genome

AF:

0.000331

AC:

AN:

151272

Hom.:

Cov.:

AF XY:

0.000298

AC XY:

AN XY:

73902

show subpopulations

Gnomad4 AFR

AF:

0.0000967

Gnomad4 AMR

AF:

0.000723

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000419

Gnomad4 FIN

AF:

0.000291

Gnomad4 NFE

AF:

0.000428

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

POU6F2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 02, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over