NM_001393986.1:c.5037-5121A>C

Variant names:

• chr1-13811306-A-C
• rs2744690
• NM_001393986.1:c.5037-5121A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393986.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM2	NM_001393986.1	MANE Select	c.5037-5121A>C		intron	N/A	NP_001380915.1
	PRDM2	NM_012231.5		c.5037-5121A>C		intron	N/A	NP_036363.2
	PRDM2	NM_001393987.1		c.4434-5121A>C		intron	N/A	NP_001380916.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM2	ENST00000311066.10	TSL:5 MANE Select	c.5037-5121A>C		intron	N/A	ENSP00000312352.6
	PRDM2	ENST00000235372.11	TSL:1	c.5037-5121A>C		intron	N/A	ENSP00000235372.6
	PRDM2	ENST00000503842.5	TSL:1	c.20-5121A>C		intron	N/A	ENSP00000425028.1

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

African (AFR) AF: 0.951 AC: 39500 AN: 41550

American (AMR) AF: 0.858 AC: 13120 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 2832 AN: 3472

East Asian (EAS) AF: 0.816 AC: 4211 AN: 5160

South Asian (SAS) AF: 0.794 AC: 3828 AN: 4822

European-Finnish (FIN) AF: 0.796 AC: 8437 AN: 10594

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.846 AC: 57551 AN: 67990

Other (OTH) AF: 0.875 AC: 1849 AN: 2114

Alfa AF: 0.854 Hom.: 92660

Bravo AF: 0.879

Asia WGS AF: 0.826 AC: 2875 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	2.8
DANN	Benign	0.42
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2744690; hg19: chr1-14137801;