dbSNP rs757747800: PRDM2:p.Ile148Lys (chr1-13749419-T-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001393986.1(PRDM2):c.443T>A(p.Ile148Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000221 in 1,355,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. I148R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

PRDM2
NM_001393986.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.50

Publications

0 publications found

Variant links:

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]

PRDM2 links:

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ACMG classification

Classification was made for transcript

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, 0.767

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRDM2	NM_001393986.1	MANE Select	c.443T>A	p.Ile148Lys	missense	Exon 6 of 10	NP_001380915.1	Q13029-1
PRDM2	NM_012231.5		c.443T>A	p.Ile148Lys	missense	Exon 6 of 10	NP_036363.2
PRDM2	NM_015866.6		c.443T>A	p.Ile148Lys	missense	Exon 6 of 9	NP_056950.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRDM2	ENST00000311066.10	TSL:5 MANE Select	c.443T>A	p.Ile148Lys	missense	Exon 6 of 10	ENSP00000312352.6	Q13029-1
PRDM2	ENST00000235372.11	TSL:1	c.443T>A	p.Ile148Lys	missense	Exon 6 of 10	ENSP00000235372.6	Q13029-1
PRDM2	ENST00000343137.8	TSL:1	c.-217T>A		5_prime_UTR	Exon 1 of 5	ENSP00000341621.4	Q13029-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000221

AC:

AN:

1355262

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

675480

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28146

American (AMR)

AF:

0.00

AC:

AN:

39700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21546

East Asian (EAS)

AF:

0.00

AC:

AN:

30794

South Asian (SAS)

AF:

0.00

AC:

AN:

83254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4804

European-Non Finnish (NFE)

AF:

0.00000287

AC:

AN:

1046478

Other (OTH)

AF:

0.00

AC:

AN:

52960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.13

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.93

MetaRNN

Pathogenic

0.77

MetaSVM

Uncertain

-0.17

MutationAssessor

Uncertain

2.1

PhyloP100

4.5

PrimateAI

Pathogenic

0.95

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.56

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.011

Polyphen

0.76

Vest4

0.76

MutPred

0.48

Gain of solvent accessibility (P = 0.0038)

MVP

0.83

MPC

0.77

ClinPred

0.85

GERP RS

3.8

PromoterAI

-0.034

Neutral

(source)

Varity_R

0.86

gMVP

0.84

Mutation Taster

=16/84

disease causing

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over