rs1203633

Positions:

• chr1-13760080-C-G
• chr1-13760080-C-T

Variant summary

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

The NM_001393986.1(PRDM2):​c.511+10593C>G 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 151,900 control chromosomes in the GnomAD database, including 2,845 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 (2845 hom., cov: 32)
• Consequence: PRDM2 NM_001393986.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.782

Genes affected

PRDM2 (HGNC:9347): (PR/SET domain 2) This tumor suppressor gene is a member of a nuclear histone/protein methyltransferase superfamily. It encodes a zinc finger protein that can bind to retinoblastoma protein, estrogen receptor, and the TPA-responsive element (MTE) of the heme-oxygenase-1 gene. Although the functions of this protein have not been fully characterized, it may (1) play a role in transcriptional regulation during neuronal differentiation and pathogenesis of retinoblastoma, (2) act as a transcriptional activator of the heme-oxygenase-1 gene, and (3) be a specific effector of estrogen action. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM2	NM_001393986.1	c.511+10593C>G		intron_variant		ENST00000311066.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM2	ENST00000311066.10	c.511+10593C>G		intron_variant		5	NM_001393986.1	P1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26301 AN: 151782 Hom.: 2845 Cov.: 32

Gnomad AFR AF: 0.0489

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.222

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: 26308 AN: 151900 Hom.: 2845 Cov.: 32 AF XY: 0.175 AC XY: 12999 AN XY: 74224

Gnomad4 AFR AF: 0.0487

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.187

Alfa AF: 0.0661 Hom.: 104

Bravo AF: 0.173

Asia WGS AF: 0.235 AC: 816 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.68

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: rs1203633; hg19: chr1-14086575;