rs12043842

Variant names:

• chr1-33393195-C-T
• rs12043842
• NM_001385109.1:c.-54-17602G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385109.1. 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
	PHC2	NM_001385109.1	MANE Select	c.-54-17602G>A		intron	N/A	NP_001372038.1	Q8IXK0-5
	PHC2	NM_001385112.1		c.-54-17602G>A		intron	N/A	NP_001372041.1	A0A994J5J9
	PHC2	NM_001385119.1		c.-54-17602G>A		intron	N/A	NP_001372048.1	Q8IXK0-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHC2	ENST00000683057.1	MANE Select	c.-54-17602G>A		intron	N/A	ENSP00000507877.1	Q8IXK0-5
	PHC2	ENST00000431992.6	TSL:1	c.-54-17602G>A		intron	N/A	ENSP00000389436.2	A0A0A0MSI2
	PHC2	ENST00000881545.1		c.-54-17602G>A		intron	N/A	ENSP00000551604.1

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

African (AFR) AF: 0.0457 AC: 1897 AN: 41526

American (AMR) AF: 0.177 AC: 2709 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 509 AN: 3470

East Asian (EAS) AF: 0.222 AC: 1148 AN: 5160

South Asian (SAS) AF: 0.268 AC: 1292 AN: 4812

European-Finnish (FIN) AF: 0.179 AC: 1892 AN: 10594

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.238 AC: 16207 AN: 67960

Other (OTH) AF: 0.189 AC: 399 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.60
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12043842; hg19: chr1-33858796;