rs12043842

Positions:

• chr1-33393195-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001385109.1(PHC2):​c.-54-17602G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,122 control chromosomes in the GnomAD database, including 2,807 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2807 hom., cov: 31)
• Consequence: PHC2 NM_001385109.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276

Genes affected

PHC2 (HGNC:3183): (polyhomeotic homolog 2) In Drosophila melanogaster, the 'Polycomb' group (PcG) of genes are part of a cellular memory system that is responsible for the stable inheritance of gene activity. PcG proteins form a large multimeric, chromatin-associated protein complex. The protein encoded by this gene has homology to the Drosophila PcG protein 'polyhomeotic' (Ph) and is known to heterodimerize with EDR1 and colocalize with BMI1 in interphase nuclei of human cells. The specific function in human cells has not yet been determined. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHC2	NM_001385109.1	c.-54-17602G>A		intron_variant		ENST00000683057.1	NP_001372038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHC2	ENST00000683057.1	c.-54-17602G>A		intron_variant			NM_001385109.1	ENSP00000507877
PHC2	ENST00000431992.6	c.-54-17602G>A		intron_variant		1		ENSP00000389436
PHC2	ENST00000373422.8	c.-54-17602G>A		intron_variant		2		ENSP00000362521

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26353 AN: 152004 Hom.: 2814 Cov.: 31

Gnomad AFR AF: 0.0458

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.190

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.173 AC: 26327 AN: 152122 Hom.: 2807 Cov.: 31 AF XY: 0.173 AC XY: 12890 AN XY: 74360

Gnomad4 AFR AF: 0.0457

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.189

Alfa AF: 0.191 Hom.: 471

Bravo AF: 0.166

Asia WGS AF: 0.208 AC: 721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12043842; hg19: chr1-33858796;