1-13778579-G-C

Variant names:

• chr1-13778579-G-C
• rs759381706
• NM_001393986.1:c.784G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001393986.1(PRDM2):​c.784G>C​(p.Glu262Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E262K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PRDM2 NM_001393986.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16683877).

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.784G>C	p.Glu262Gln	missense	Exon 8 of 10	NP_001380915.1	Q13029-1
	PRDM2	NM_012231.5		c.784G>C	p.Glu262Gln	missense	Exon 8 of 10	NP_036363.2
	PRDM2	NM_015866.6		c.784G>C	p.Glu262Gln	missense	Exon 8 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.784G>C	p.Glu262Gln	missense	Exon 8 of 10	ENSP00000312352.6	Q13029-1
	PRDM2	ENST00000235372.11	TSL:1	c.784G>C	p.Glu262Gln	missense	Exon 8 of 10	ENSP00000235372.6	Q13029-1
	PRDM2	ENST00000343137.8	TSL:1	c.181G>C	p.Glu61Gln	missense	Exon 4 of 5	ENSP00000341621.4	Q13029-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.035
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.7
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.11
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.087	T
Polyphen		0.30	B
Vest4		0.072
MutPred		0.24		Gain of loop (P = 0.2045)
MVP		0.57
MPC		0.64
ClinPred		0.67	D
GERP RS		5.7
Varity_R		0.24
gMVP		0.10
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs759381706; hg19: chr1-14105074;