1-13814849-T-C

Variant names:

• chr1-13814849-T-C
• rs2235515
• NM_001393986.1:c.5037-1578T>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.5037-1578T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,094 control chromosomes in the GnomAD database, including 35,662 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 0.67 (35662 hom., cov: 32)
• Consequence: PRDM2 NM_001393986.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110
• Publications: 7 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM2	NM_001393986.1	c.5037-1578T>C		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.5037-1578T>C		intron_variant	Intron 8 of 9	5	NM_001393986.1	ENSP00000312352.6

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102417 AN: 151976 Hom.: 35630 Cov.: 32

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.674 AC: 102489 AN: 152094 Hom.: 35662 Cov.: 32 AF XY: 0.674 AC XY: 50101 AN XY: 74368

African (AFR) AF: 0.500 AC: 20753 AN: 41474

American (AMR) AF: 0.747 AC: 11418 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 2535 AN: 3468

East Asian (EAS) AF: 0.552 AC: 2841 AN: 5146

South Asian (SAS) AF: 0.565 AC: 2725 AN: 4824

European-Finnish (FIN) AF: 0.775 AC: 8212 AN: 10592

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51677 AN: 67980

Other (OTH) AF: 0.691 AC: 1460 AN: 2112

Alfa AF: 0.644 Hom.: 2267

Bravo AF: 0.667

Asia WGS AF: 0.575 AC: 2000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		-0.011
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2235515; hg19: chr1-14141344;