NM_001393986.1:c.5037-3096C>T

Variant names:

• chr1-13813331-C-T
• rs2245218
• NM_001393986.1:c.5037-3096C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393986.1(PRDM2):​c.5037-3096C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 152,098 control chromosomes in the GnomAD database, including 56,001 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 0.86 (56001 hom., cov: 30)
• Consequence: PRDM2 NM_001393986.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM2	NM_001393986.1	MANE Select	c.5037-3096C>T		intron	N/A	NP_001380915.1	Q13029-1
	PRDM2	NM_012231.5		c.5037-3096C>T		intron	N/A	NP_036363.2
	PRDM2	NM_001393987.1		c.4434-3096C>T		intron	N/A	NP_001380916.1	Q13029-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM2	ENST00000311066.10	TSL:5 MANE Select	c.5037-3096C>T		intron	N/A	ENSP00000312352.6	Q13029-1
	PRDM2	ENST00000235372.11	TSL:1	c.5037-3096C>T		intron	N/A	ENSP00000235372.6	Q13029-1
	PRDM2	ENST00000503842.5	TSL:1	c.20-3096C>T		intron	N/A	ENSP00000425028.1	D6RED5

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130033 AN: 151980 Hom.: 55937 Cov.: 30

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.849

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

GnomAD4 genome AF: 0.856 AC: 130154 AN: 152098 Hom.: 56001 Cov.: 30 AF XY: 0.852 AC XY: 63332 AN XY: 74340

African (AFR) AF: 0.938 AC: 38963 AN: 41528

American (AMR) AF: 0.856 AC: 13085 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 2733 AN: 3472

East Asian (EAS) AF: 0.691 AC: 3559 AN: 5152

South Asian (SAS) AF: 0.748 AC: 3591 AN: 4802

European-Finnish (FIN) AF: 0.795 AC: 8397 AN: 10562

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.839 AC: 57018 AN: 67974

Other (OTH) AF: 0.851 AC: 1797 AN: 2112

Alfa AF: 0.847 Hom.: 79744

Bravo AF: 0.864

Asia WGS AF: 0.783 AC: 2723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.59
PhyloP100		1.6
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: rs2245218; hg19: chr1-14139826;