rs202234462

Variant names:

• chr7-39451627-C-A
• rs202234462
• NM_001370959.1:c.1415C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-39451627-C-A
• chr7-39451627-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001370959.1(POU6F2):​c.1415C>A​(p.Pro472His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. P472L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: POU6F2 NM_001370959.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.64
• Publications: 0 publications found

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]

YAE1-DT (HGNC:55820): (YAE1 divergent transcript)

LOC105375238 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU6F2	NM_001370959.1	MANE Select	c.1415C>A	p.Pro472His	missense	Exon 8 of 10	NP_001357888.1	A0A6E1XZL4
	POU6F2	NM_007252.4		c.1328C>A	p.Pro443His	missense	Exon 9 of 11	NP_009183.3	P78424-1
	POU6F2	NM_001166018.2		c.1328C>A	p.Pro443His	missense	Exon 9 of 11	NP_001159490.1	P78424-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU6F2	ENST00000518318.7	TSL:1 MANE Select	c.1415C>A	p.Pro472His	missense	Exon 8 of 10	ENSP00000430514.3	A0A6E1XZL4
	POU6F2	ENST00000403058.6	TSL:5	c.1328C>A	p.Pro443His	missense	Exon 9 of 11	ENSP00000384004.1	P78424-1
	POU6F2	ENST00000524147.5	TSL:5	n.1411C>A		non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	D
Eigen	Uncertain	0.63
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	0.81	L
PhyloP100		5.6
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.13		Gain of MoRF binding (P = 0.0436)
MVP		0.96
MPC		0.15
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.49
gMVP		0.79
Mutation Taster		=65/35	polymorphism

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

Other links and lift over

dbSNP: rs202234462; hg19: chr7-39491226;