7-38978015-C-G

Position:

• chr7-38978015-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001370959.1(POU6F2):​c.62C>G​(p.Ser21Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: POU6F2 NM_001370959.1 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.69

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-38978015-C-G is Pathogenic according to our data. Variant chr7-38978015-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 1872.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU6F2	NM_001370959.1	c.62C>G	p.Ser21Ter	stop_gained	1/10	ENST00000518318.7
POU6F2	NM_001166018.2	c.-137C>G		5_prime_UTR_variant	1/11
POU6F2	NM_007252.4	c.-137C>G		5_prime_UTR_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU6F2	ENST00000518318.7	c.62C>G	p.Ser21Ter	stop_gained	1/10	1	NM_001370959.1	P2
POU6F2	ENST00000403058.6	c.-137C>G		5_prime_UTR_variant	1/11	5		A2
POU6F2	ENST00000673891.1	c.62C>G	p.Ser21Ter	stop_gained, NMD_transcript_variant	1/11
POU6F2	ENST00000674059.1	c.62C>G	p.Ser21Ter	stop_gained, NMD_transcript_variant	1/11

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Wilms tumor 5 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Pathogenic	37
DANN	Benign	0.87

Splicing

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: chr7-39017615;