NM_001393986.1:c.459G>C

Variant names:

• chr1-13749435-G-C
• rs756547427
• NM_001393986.1:c.459G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001393986.1(PRDM2):​c.459G>C​(p.Glu153Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRDM2 NM_001393986.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.89
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36468834).

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.459G>C	p.Glu153Asp	missense	Exon 6 of 10	NP_001380915.1	Q13029-1
	PRDM2	NM_012231.5		c.459G>C	p.Glu153Asp	missense	Exon 6 of 10	NP_036363.2
	PRDM2	NM_015866.6		c.459G>C	p.Glu153Asp	missense	Exon 6 of 9	NP_056950.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM2	ENST00000311066.10	TSL:5 MANE Select	c.459G>C	p.Glu153Asp	missense	Exon 6 of 10	ENSP00000312352.6	Q13029-1
	PRDM2	ENST00000235372.11	TSL:1	c.459G>C	p.Glu153Asp	missense	Exon 6 of 10	ENSP00000235372.6	Q13029-1
	PRDM2	ENST00000343137.8	TSL:1	c.-201G>C		5_prime_UTR	Exon 1 of 5	ENSP00000341621.4	Q13029-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.19
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.88	D
MetaRNN	Benign	0.36	T
MetaSVM	Uncertain	-0.060	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.9
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.22
Sift	Benign	0.039	D
Sift4G	Benign	0.18	T
Polyphen		0.27	B
Vest4		0.29
MutPred		0.22		Loss of helix (P = 0.0068)
MVP		0.69
MPC		0.22
ClinPred		0.75	D
GERP RS		3.8
PromoterAI		-0.28	Neutral
Varity_R		0.29
gMVP		0.46
Mutation Taster		=194/106	polymorphism

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: rs756547427; hg19: chr1-14075930;