1-13799001-G-C

Variant names:

• chr1-13799001-G-C
• rs2697992
• NM_001393986.1:c.5036+16170G>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.5036+16170G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,134 control chromosomes in the GnomAD database, including 46,934 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 0.78 (46934 hom., cov: 32)
• Consequence: PRDM2 NM_001393986.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM2	NM_001393986.1	c.5036+16170G>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.5036+16170G>C		intron_variant	Intron 8 of 9	5	NM_001393986.1	ENSP00000312352.6

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118583 AN: 152016 Hom.: 46869 Cov.: 32

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.860

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.780 AC: 118709 AN: 152134 Hom.: 46934 Cov.: 32 AF XY: 0.779 AC XY: 57889 AN XY: 74342

African (AFR) AF: 0.907 AC: 37682 AN: 41536

American (AMR) AF: 0.780 AC: 11919 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.741 AC: 2574 AN: 3472

East Asian (EAS) AF: 0.860 AC: 4450 AN: 5176

South Asian (SAS) AF: 0.693 AC: 3336 AN: 4816

European-Finnish (FIN) AF: 0.686 AC: 7228 AN: 10544

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48940 AN: 67994

Other (OTH) AF: 0.797 AC: 1682 AN: 2110

Alfa AF: 0.640 Hom.: 1727

Bravo AF: 0.797

Asia WGS AF: 0.802 AC: 2789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.31
DANN	Benign	0.35
PhyloP100		-0.80
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: rs2697992; hg19: chr1-14125496; COSMIC: COSV52454961;