Variant 7-39339681-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001370959.1(POU6F2):c.638T>G(p.Leu213Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000987 in 1,601,858 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00095 ( 1 hom. )

Consequence

POU6F2
NM_001370959.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 6.37

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.008406937).

BP6

Variant 7-39339681-T-G is Benign according to our data. Variant chr7-39339681-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 713595.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 201 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU6F2	NM_001370959.1 linkuse as main transcript	c.638T>G	p.Leu213Arg	missense_variant	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.638T>G	p.Leu213Arg	missense_variant	5/10	1	NM_001370959.1	ENSP00000430514	P2

Frequencies

GnomAD3 genomes

AF:

0.00132

AC:

200

AN:

151944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000853

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00748

Gnomad FIN

AF:

0.00368

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00144

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000795

AC:

187

AN:

235256

Hom.:

AF XY:

0.000975

AC XY:

125

AN XY:

128164

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000263

Gnomad ASJ exome

AF:

0.000627

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00371

Gnomad FIN exome

AF:

0.00149

Gnomad NFE exome

AF:

0.000309

Gnomad OTH exome

AF:

0.00102

GnomAD4 exome

AF:

0.000952

AC:

1380

AN:

1449796

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

832

AN XY:

721262

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000583

Gnomad4 ASJ exome

AF:

0.000695

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00641

Gnomad4 FIN exome

AF:

0.00214

Gnomad4 NFE exome

AF:

0.000560

Gnomad4 OTH exome

AF:

0.000864

GnomAD4 genome

AF:

0.00132

AC:

201

AN:

152062

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

113

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000852

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00770

Gnomad4 FIN

AF:

0.00368

Gnomad4 NFE

AF:

0.00144

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000674

Hom.:

ExAC

AF:

0.000548

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 17, 2018

- -

POU6F2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 12, 2023

This variant is classified as likely 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

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.095

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.053

T;.;.;.;.

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.48

T;T;T;T;T

M_CAP

Benign

0.075

MetaRNN

Benign

0.0084

T;T;T;T;T

MetaSVM

Benign

-0.30

MutationAssessor

Benign

0.34

N;N;.;.;.

MutationTaster

Benign

0.96

D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

0.27

N;N;N;N;N

REVEL

Uncertain

0.30

Sift

Benign

0.050

D;D;T;D;D

Sift4G

Benign

0.38

T;T;T;T;T

Polyphen

0.99

D;D;.;.;.

Vest4

0.71

MVP

0.90

MPC

0.19

ClinPred

0.079

GERP RS

4.5

Varity_R

0.31

gMVP

0.14

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

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