rs2744690

chr1-13811306-A-C

Variant summary

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

The NM_001393986.1(PRDM2):c.5037-5121A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 152,200 control chromosomes in the GnomAD database, including 57,801 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 0.87 (57801 hom., cov: 32)
• Consequence: PRDM2 NM_001393986.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM2	NM_001393986.1	c.5037-5121A>C		intron_variant		ENST00000311066.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM2	ENST00000311066.10	c.5037-5121A>C		intron_variant		5	NM_001393986.1	P1

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132234 AN: 152082 Hom.: 57738 Cov.: 32

Gnomad AFR AF: 0.951

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.873

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

GnomAD4 genome AF: 0.870 AC: 132354 AN: 152200 Hom.: 57801 Cov.: 32 AF XY: 0.867 AC XY: 64510 AN XY: 74404

Gnomad4 AFR AF: 0.951

Gnomad4 AMR AF: 0.858

Gnomad4 ASJ AF: 0.816

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.794

Gnomad4 FIN AF: 0.796

Gnomad4 NFE AF: 0.846

Gnomad4 OTH AF: 0.875

Alfa AF: 0.851 Hom.: 72405

Bravo AF: 0.879

Asia WGS AF: 0.826 AC: 2875 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	2.8
Dann	Benign	0.42

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: rs2744690; hg19: chr1-14137801;