Genetic Variant POU6F2:p.Ala40Gly (chr7-39085873-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001370959.1(POU6F2):c.119C>G(p.Ala40Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A40D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Consequence

POU6F2
NM_001370959.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.23

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

Wilms tumor 5
Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

POU6F2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34351227).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POU6F2	NM_001370959.1	MANE Select	c.119C>G	p.Ala40Gly	missense	Exon 2 of 10	NP_001357888.1	A0A6E1XZL4
POU6F2	NM_007252.4		c.32C>G	p.Ala11Gly	missense	Exon 3 of 11	NP_009183.3	P78424-1
POU6F2	NM_001166018.2		c.32C>G	p.Ala11Gly	missense	Exon 3 of 11	NP_001159490.1	P78424-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POU6F2	ENST00000518318.7	TSL:1 MANE Select	c.119C>G	p.Ala40Gly	missense	Exon 2 of 10	ENSP00000430514.3	A0A6E1XZL4
POU6F2	ENST00000403058.6	TSL:5	c.32C>G	p.Ala11Gly	missense	Exon 3 of 11	ENSP00000384004.1	P78424-1
POU6F2	ENST00000451021.5	TSL:4	n.171C>G		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.035

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.77

M_CAP

Benign

0.034

MetaRNN

Benign

0.34

MetaSVM

Uncertain

-0.12

MutationAssessor

Benign

0.34

PhyloP100

7.2

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.34

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.036

Polyphen

0.62

Vest4

0.45

MutPred

0.063

Gain of methylation at K16 (P = 0.1374)

MVP

0.94

MPC

0.57

ClinPred

0.97

GERP RS

5.5

Varity_R

0.35

gMVP

0.091

Mutation Taster

=76/24

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over