7-39085902-G-C

Position:

• chr7-39085902-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370959.1(POU6F2):​c.148G>C​(p.Val50Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: POU6F2 NM_001370959.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.15

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14269).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU6F2	NM_001370959.1	c.148G>C	p.Val50Leu	missense_variant	2/10	ENST00000518318.7	NP_001357888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU6F2	ENST00000518318.7	c.148G>C	p.Val50Leu	missense_variant	2/10	1	NM_001370959.1	ENSP00000430514	P2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 30, 2024

The c.61G>C (p.V21L) alteration is located in exon 3 (coding exon 2) of the POU6F2 gene. This alteration results from a G to C substitution at nucleotide position 61, causing the valine (V) at amino acid position 21 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.054	T;.;.;.;.;.
Eigen	Benign	-0.27
Eigen_PC	Benign	0.0020
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.68	T;T;T;T;T;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.14	T;T;T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	-0.20	N;N;.;.;.;.
MutationTaster	Benign	0.98	N;N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.39	N;N;N;N;N;N
REVEL	Uncertain	0.30
Sift	Benign	0.35	T;T;T;T;T;T
Sift4G	Benign	0.71	T;T;T;T;T;T
Polyphen		0.0	B;B;.;.;.;.
Vest4		0.10
MutPred		0.090		Loss of catalytic residue at V21 (P = 0.0094);Loss of catalytic residue at V21 (P = 0.0094);.;.;.;.;
MVP		0.75
MPC		0.13
ClinPred		0.86	D
GERP RS		4.5
Varity_R		0.19
gMVP		0.073

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-39125502;