1-13814849-T-C

Position:

• chr1-13814849-T-C

Variant summary

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

The NM_001393986.1(PRDM2):​c.5037-1578T>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

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=-0.84).
• 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/exons	MANE	UniProt
PRDM2	NM_001393986.1	c.5037-1578T>C		intron_variant		ENST00000311066.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM2	ENST00000311066.10	c.5037-1578T>C		intron_variant		5	NM_001393986.1	P1

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

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.731

Gnomad4 EAS AF: 0.552

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.775

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.691

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2235515; hg19: chr1-14141344;