chr1-13749419-T-G

Variant names:

• chr1-13749419-T-G
• rs757747800
• NM_001393986.1:c.443T>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001393986.1(PRDM2):​c.443T>G​(p.Ile148Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000738 in 1,355,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: PRDM2 NM_001393986.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.50
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.75

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.443T>G	p.Ile148Arg	missense	Exon 6 of 10	NP_001380915.1	Q13029-1
	PRDM2	NM_012231.5		c.443T>G	p.Ile148Arg	missense	Exon 6 of 10	NP_036363.2
	PRDM2	NM_015866.6		c.443T>G	p.Ile148Arg	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.443T>G	p.Ile148Arg	missense	Exon 6 of 10	ENSP00000312352.6	Q13029-1
	PRDM2	ENST00000235372.11	TSL:1	c.443T>G	p.Ile148Arg	missense	Exon 6 of 10	ENSP00000235372.6	Q13029-1
	PRDM2	ENST00000343137.8	TSL:1	c.-217T>G		5_prime_UTR	Exon 1 of 5	ENSP00000341621.4	Q13029-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000442 AC: 1 AN: 226046 AF XY: 0.00000802

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000319

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.38e-7 AC: 1 AN: 1355260 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 675478

African (AFR) AF: 0.00 AC: 0 AN: 28146

American (AMR) AF: 0.0000252 AC: 1 AN: 39700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21546

East Asian (EAS) AF: 0.00 AC: 0 AN: 30794

South Asian (SAS) AF: 0.00 AC: 0 AN: 83254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4804

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1046476

Other (OTH) AF: 0.00 AC: 0 AN: 52960

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

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	0.98
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.92	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.5
PrimateAI	Pathogenic	0.95	D
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.010	D
Polyphen		0.99	D
Vest4		0.71
MutPred		0.40		Gain of disorder (P = 0.0405)
MVP		0.78
MPC		0.88
ClinPred		0.91	D
GERP RS		3.8
PromoterAI		0.069	Neutral
Varity_R		0.84
gMVP		0.81
Mutation Taster		=16/84	disease causing

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: rs757747800; hg19: chr1-14075914;