rs11580688

Variant names:

• chr1-13790733-G-A
• rs11580688
• NM_001393986.1:c.5036+7902G>A

Variant summary

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

The NM_001393986.1(PRDM2):​c.5036+7902G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 143,940 control chromosomes in the GnomAD database, including 3,553 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 0.21 (3553 hom., cov: 32)
• Consequence: PRDM2 NM_001393986.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.65
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM2	NM_001393986.1	c.5036+7902G>A		intron_variant	Intron 8 of 9	ENST00000311066.10	NP_001380915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM2	ENST00000311066.10	c.5036+7902G>A		intron_variant	Intron 8 of 9	5	NM_001393986.1	ENSP00000312352.6

Frequencies

GnomAD3 genomes AF: 0.207 AC: 29790 AN: 143836 Hom.: 3555 Cov.: 32

Gnomad AFR AF: 0.0707

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.207 AC: 29782 AN: 143940 Hom.: 3553 Cov.: 32 AF XY: 0.203 AC XY: 14268 AN XY: 70270

African (AFR) AF: 0.0705 AC: 2835 AN: 40198

American (AMR) AF: 0.231 AC: 3271 AN: 14162

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 898 AN: 3350

East Asian (EAS) AF: 0.146 AC: 707 AN: 4848

South Asian (SAS) AF: 0.142 AC: 589 AN: 4142

European-Finnish (FIN) AF: 0.237 AC: 2397 AN: 10106

Middle Eastern (MID) AF: 0.266 AC: 74 AN: 278

European-Non Finnish (NFE) AF: 0.287 AC: 18373 AN: 64078

Other (OTH) AF: 0.240 AC: 477 AN: 1988

Alfa AF: 0.248 Hom.: 4281

Bravo AF: 0.192

Asia WGS AF: 0.113 AC: 394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.016
DANN	Benign	0.64
PhyloP100		-3.7
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: rs11580688; hg19: chr1-14117228;