rs41269807

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001393986.1(PRDM2):​c.3070T>A​(p.Ser1024Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0413 in 1,610,400 control chromosomes in the GnomAD database, including 1,547 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 116 hom., cov: 30)
Exomes 𝑓: 0.042 ( 1431 hom. )

Consequence

PRDM2
NM_001393986.1 missense

Scores

6
12

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.47
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.00453192).
BP6
Variant 1-13780865-T-A is Benign according to our data. Variant chr1-13780865-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 403342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0312 (4710/150756) while in subpopulation NFE AF= 0.0467 (3166/67732). AF 95% confidence interval is 0.0454. There are 116 homozygotes in gnomad4. There are 2255 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
High AC in GnomAd4 at 4710 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PRDM2NM_001393986.1 linkuse as main transcriptc.3070T>A p.Ser1024Thr missense_variant 8/10 ENST00000311066.10 NP_001380915.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PRDM2ENST00000311066.10 linkuse as main transcriptc.3070T>A p.Ser1024Thr missense_variant 8/105 NM_001393986.1 ENSP00000312352 P1Q13029-1

Frequencies

GnomAD3 genomes
AF:
0.0313
AC:
4708
AN:
150640
Hom.:
116
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00847
Gnomad AMI
AF:
0.00549
Gnomad AMR
AF:
0.0348
Gnomad ASJ
AF:
0.0470
Gnomad EAS
AF:
0.000588
Gnomad SAS
AF:
0.0360
Gnomad FIN
AF:
0.0241
Gnomad MID
AF:
0.0224
Gnomad NFE
AF:
0.0468
Gnomad OTH
AF:
0.0336
GnomAD3 exomes
AF:
0.0346
AC:
8686
AN:
251014
Hom.:
184
AF XY:
0.0366
AC XY:
4962
AN XY:
135622
show subpopulations
Gnomad AFR exome
AF:
0.00744
Gnomad AMR exome
AF:
0.0225
Gnomad ASJ exome
AF:
0.0461
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.0381
Gnomad FIN exome
AF:
0.0266
Gnomad NFE exome
AF:
0.0470
Gnomad OTH exome
AF:
0.0403
GnomAD4 exome
AF:
0.0423
AC:
61765
AN:
1459644
Hom.:
1431
Cov.:
53
AF XY:
0.0421
AC XY:
30559
AN XY:
726252
show subpopulations
Gnomad4 AFR exome
AF:
0.00703
Gnomad4 AMR exome
AF:
0.0232
Gnomad4 ASJ exome
AF:
0.0445
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.0394
Gnomad4 FIN exome
AF:
0.0274
Gnomad4 NFE exome
AF:
0.0466
Gnomad4 OTH exome
AF:
0.0399
GnomAD4 genome
AF:
0.0312
AC:
4710
AN:
150756
Hom.:
116
Cov.:
30
AF XY:
0.0307
AC XY:
2255
AN XY:
73570
show subpopulations
Gnomad4 AFR
AF:
0.00845
Gnomad4 AMR
AF:
0.0348
Gnomad4 ASJ
AF:
0.0470
Gnomad4 EAS
AF:
0.000590
Gnomad4 SAS
AF:
0.0365
Gnomad4 FIN
AF:
0.0241
Gnomad4 NFE
AF:
0.0467
Gnomad4 OTH
AF:
0.0332
Alfa
AF:
0.0434
Hom.:
127
Bravo
AF:
0.0303
TwinsUK
AF:
0.0520
AC:
193
ALSPAC
AF:
0.0402
AC:
155
ESP6500AA
AF:
0.00749
AC:
33
ESP6500EA
AF:
0.0451
AC:
388
ExAC
AF:
0.0351
AC:
4258
Asia WGS
AF:
0.0140
AC:
50
AN:
3478
EpiCase
AF:
0.0486
EpiControl
AF:
0.0470

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 29, 2016Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
not provided Benign:1
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.49
CADD
Uncertain
23
DANN
Benign
0.95
DEOGEN2
Benign
0.084
.;T;.;.
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.85
D;D;.;T
MetaRNN
Benign
0.0045
T;T;T;T
MetaSVM
Benign
-0.74
T
MutationAssessor
Uncertain
2.4
M;M;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-0.87
N;N;N;N
REVEL
Benign
0.17
Sift
Uncertain
0.0030
D;D;D;D
Sift4G
Benign
0.089
T;T;T;T
Polyphen
0.86
P;P;.;.
Vest4
0.24
MPC
0.17
ClinPred
0.033
T
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.26
gMVP
0.47

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs41269807; hg19: chr1-14107360; COSMIC: COSV52446694; COSMIC: COSV52446694; API