Variant chr7-39339687-T-A 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.644T>A(p.Leu215His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,600,800 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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: 0.0012 ( 9 hom. )

Consequence

POU6F2
NM_001370959.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.46

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=0.0053934455).

BP6

Variant 7-39339687-T-A is Benign according to our data. Variant chr7-39339687-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 713596.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 203 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU6F2	NM_001370959.1 linkuse as main transcript	c.644T>A	p.Leu215His	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.644T>A	p.Leu215His	missense_variant	5/10	1	NM_001370959.1	ENSP00000430514	P2

Frequencies

GnomAD3 genomes

AF:

0.00133

AC:

202

AN:

151692

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000920

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00755

Gnomad FIN

AF:

0.00370

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00146

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00140

AC:

330

AN:

235718

Hom.:

AF XY:

0.00170

AC XY:

219

AN XY:

128552

show subpopulations

Gnomad AFR exome

AF:

0.000133

Gnomad AMR exome

AF:

0.000557

Gnomad ASJ exome

AF:

0.000725

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00666

Gnomad FIN exome

AF:

0.00145

Gnomad NFE exome

AF:

0.000664

Gnomad OTH exome

AF:

0.00170

GnomAD4 exome

AF:

0.00117

AC:

1695

AN:

1448990

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

979

AN XY:

720786

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000632

Gnomad4 ASJ exome

AF:

0.000694

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00724

Gnomad4 FIN exome

AF:

0.00207

Gnomad4 NFE exome

AF:

0.000769

Gnomad4 OTH exome

AF:

0.000981

GnomAD4 genome

AF:

0.00134

AC:

203

AN:

151810

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

114

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000919

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00776

Gnomad4 FIN

AF:

0.00370

Gnomad4 NFE

AF:

0.00146

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00127

Hom.:

ExAC

AF:

0.000764

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.081

T;.;.;.;.

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.53

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.33

T;T;T;T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.0054

T;T;T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.0

N;N;.;.;.

MutationTaster

Benign

0.69

D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.44

N;N;N;N;N

REVEL

Benign

0.17

Sift

Uncertain

0.013

D;D;D;D;D

Sift4G

Benign

0.091

T;T;T;T;T

Polyphen

0.0

B;B;.;.;.

Vest4

0.47

MVP

0.80

MPC

0.16

ClinPred

0.025

GERP RS

1.9

Varity_R

0.12

gMVP

0.29

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