7-39339688-C-G

Position:

• chr7-39339688-C-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001370959.1(POU6F2):​c.645C>G​(p.Leu215=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 151,450 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (9 hom.)
  • Failed GnomAD Quality Control
• Consequence: POU6F2 NM_001370959.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.566

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 Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 7-39339688-C-G is Benign according to our data. Variant chr7-39339688-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 713597.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.566 with no splicing effect.
• BS2: High AC in GnomAd4 at 205 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU6F2	NM_001370959.1	c.645C>G	p.Leu215=	synonymous_variant	5/10	ENST00000518318.7	NP_001357888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU6F2	ENST00000518318.7	c.645C>G	p.Leu215=	synonymous_variant	5/10	1	NM_001370959.1	ENSP00000430514	P2

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 204 AN: 151338 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000921

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00774

Gnomad FIN AF: 0.00375

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00148

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00199 AC: 324 AN: 163196 Hom.: 3 AF XY: 0.00239 AC XY: 212 AN XY: 88804

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000870

Gnomad ASJ exome AF: 0.00112

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00972

Gnomad FIN exome AF: 0.00205

Gnomad NFE exome AF: 0.000937

Gnomad OTH exome AF: 0.00285

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00137 AC: 1981 AN: 1446464 Hom.: 9 Cov.: 32 AF XY: 0.00155 AC XY: 1113 AN XY: 719466

Gnomad4 AFR exome AF: 0.000180

Gnomad4 AMR exome AF: 0.000633

Gnomad4 ASJ exome AF: 0.000773

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00761

Gnomad4 FIN exome AF: 0.00213

Gnomad4 NFE exome AF: 0.000975

Gnomad4 OTH exome AF: 0.00132

GnomAD4 genome AF: 0.00135 AC: 205 AN: 151450 Hom.: 1 Cov.: 32 AF XY: 0.00157 AC XY: 116 AN XY: 74002

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.000920

Gnomad4 ASJ AF: 0.000866

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00795

Gnomad4 FIN AF: 0.00375

Gnomad4 NFE AF: 0.00148

Gnomad4 OTH AF: 0.00143

Alfa AF: 0.00172 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.8
DANN	Benign	0.66

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

Other links and lift over

dbSNP: rs575735871; hg19: chr7-39379287;